392 results on '"Atherosclerosis microbiology"'
Search Results
102. Current State of Knowledge on Implications of Gut Microbiome for Surgical Conditions.
- Author
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Chen EB, Cason C, Gilbert JA, and Ho KJ
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- Anastomotic Leak microbiology, Anastomotic Leak surgery, Atherosclerosis microbiology, Colorectal Neoplasms surgery, Humans, Inflammatory Bowel Diseases microbiology, Inflammatory Bowel Diseases surgery, Non-alcoholic Fatty Liver Disease surgery, Obesity surgery, Colorectal Neoplasms microbiology, Gastrointestinal Microbiome, Non-alcoholic Fatty Liver Disease microbiology, Obesity microbiology
- Abstract
The role of the microbiome in human health has become a central tenant of current medical research, infiltrating a diverse disciplinary base whereby microbiology, computer science, ecology, gastroenterology, immunology, neurophysiology and psychology, metabolism, and cardiovascular medicine all intersect. Traditionally, commensal gut microbiota have been assumed to play a significant role only in the metabolic processing of dietary nutrients and host metabolites, the fortification of gut epithelial barrier function, and the development of mucosal immunity. However, over the last 20 years, new technologies and renewed interest have uncovered a considerably broader influence of the microbiota on health maintenance and disease development, many of which are of particular relevance for surgeons. This article provides a broad overview of the current state of knowledge and a review of the technology that helped in their formation.
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- 2018
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103. Long-term Western diet fed apolipoprotein E-deficient rats exhibit only modest early atherosclerotic characteristics.
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Rune I, Rolin B, Lykkesfeldt J, Nielsen DS, Krych Ł, Kanter JE, Bornfeldt KE, Kihl P, Buschard K, Josefsen K, Fels JJ, Mortensen A, Christoffersen B, Kirk RK, and Hansen AK
- Subjects
- Animals, Aorta drug effects, Aorta pathology, Atherosclerosis microbiology, Body Weight drug effects, Diet, High-Fat adverse effects, Female, Gastrointestinal Microbiome, Insulin Resistance, Liver pathology, Oxidative Stress drug effects, Rats, Time Factors, Apolipoproteins E deficiency, Atherosclerosis metabolism, Atherosclerosis pathology, Diet, Western adverse effects
- Abstract
In the apolipoprotein E-deficient mouse, the gut microbiota has an impact on the development of atherosclerosis, but whether such correlations are also present in rats requires investigation. Therefore, we studied female SD-Apoe
tm1sage (Apoe-/- ) rats fed either a Western diet or a low-fat control diet with or without gluten, which is known to promote gut microbiota changes, until 20 weeks of age. We hypothesized that the manifestation of atherosclerosis would be more severe in Apoe-/- rats fed the Western high-fat diet, as compared with rats fed the low-fat diet, and that atherosclerosis would be accelerated by gluten. Both Western diet-feeding and gluten resulted in significant changes in gut microbiota, but the microbiota impact of gluten was transient. Compared with Apoe-/- rats fed a low-fat diet, Western diet-fed Apoe-/- rats were heavier and became glucose intolerant with increased levels of oxidative stress. They developed early fatty streak lesions in their aortic sinus, while there was no evidence of atherosclerosis in the thoracic aorta. No conclusions could be made on the impact of gluten on atherosclerosis. Although Western diet-fed Apoe-/- rats exhibited a more human-like LDL dominated blood lipid profile, signs of obesity, type 2 diabetes and cardiovascular disease were modest.- Published
- 2018
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104. Investigation of Chlamydia pneumoniae infection in Moroccan patients suffering from cardiovascular diseases.
- Author
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Yazouli LE, Hejaji H, Elmdaghri N, Alami AA, Dakka N, and Radouani F
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- Antibodies, Bacterial blood, Atherosclerosis epidemiology, Atherosclerosis microbiology, Cardiovascular Diseases diagnosis, Cardiovascular Diseases microbiology, Chlamydophila Infections blood, Chlamydophila Infections diagnosis, Chlamydophila pneumoniae immunology, Chlamydophila pneumoniae isolation & purification, DNA, Bacterial genetics, Female, Humans, Leukocytes, Mononuclear microbiology, Male, Middle Aged, Molecular Diagnostic Techniques, Polymerase Chain Reaction, Prevalence, Risk Factors, Cardiovascular Diseases epidemiology, Chlamydophila Infections epidemiology, Chlamydophila pneumoniae genetics
- Abstract
Chlamydia pneumoniae is an intracellular bacterium responsible for respiratory diseases and is highly involved in cardiovascular disease development, mainly atherosclerosis. The main objective of our study was to evaluate C. pneumoniae prevalence in Moroccan patients suffering from cardiovascular diseases. A total of 115 patients with cardiovascular diseases were enrolled, and their clinical and behavioral information was recorded. Blood was sampled from all patients as well as the atheroma plaques from 36 patients undergoing surgery. Nested PCR was performed for C. pneumoniae DNA detection in both peripheral blood mononuclear cells (PBMCs) and atheroma plaques. Statistical analysis was performed using EpiInfo software. Data analysis showed cardiovascular disease dominance in men, with a sex ratio M/F of 3.4, a majority of tobacco users (52.2%), and many diabetics (44.3%). A significant difference between genders was shown for tobacco use (p<0.05). Positive cases for PBMCs and atheroma plaques were 61% and 86%, respectively, and a significant difference between PBMCs and atheroma plaque infection was identified (p=0.02). Data analysis also showed that 12% of patients presented only C. pneumoniae infection as a risk factor. Therefore, the high prevalence of C. pneumoniae suggests its involvement in atherosclerosis, and further investigation is recommended for confirmation., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2018
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105. Two-dimensional and three-dimensional models for studying atherosclerosis pathogenesis induced by periodontopathogenic microorganisms.
- Author
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Gualtero DF, Lafaurie GI, and Fontanilla MR
- Subjects
- Antigens, Bacterial immunology, Cell Culture Techniques methods, Endothelial Cells immunology, Endothelial Cells microbiology, Endothelial Cells pathology, Endothelium, Vascular immunology, Endothelium, Vascular microbiology, Endothelium, Vascular pathology, Humans, In Vitro Techniques, Lipopolysaccharides immunology, Macrophages, Monocytes, Periodontal Diseases pathology, Periodontitis microbiology, Periodontitis pathology, Porphyromonas gingivalis immunology, Porphyromonas gingivalis pathogenicity, Atherosclerosis microbiology, Atherosclerosis pathology, Bacteria pathogenicity, Periodontal Diseases microbiology
- Abstract
Epidemiological studies have established a clinical association between periodontal disease and atherosclerosis. Bacteremia and endotoxemia episodes in patients with periodontitis appear to link these two diseases by inducing a body-wide production of cardiovascular markers. The presence of oral bacteria in atherosclerotic lesions in patients with periodontitis suggests that bacteria, or their antigenic components, induce alterations in the endothelium associated with atherosclerosis. Therefore, a causal mechanism explaining the association between both diseases can be constructed using in vitro models. This review presents current experimental approaches based on in vitro cell models used to shed light on the mechanism by which periodontal pathogenic microorganisms, and their antigenic components, induce proatherosclerotic endothelial activity. Monolayer cultures of endothelial vascular or arterial cells have been used to assess periodontal pathogenic bacteria and their antigenic compounds and endothelial activation. However, these models are not capable of reflecting the physiological characteristics of the endothelium inside vascularized tissue. Therefore, the shift from two-dimensional (2D) cellular models toward three-dimensional (3D) models of endothelial cells resembling an environment close to the physiological environment of the endothelial cell within the endothelium is useful for evaluating the physiological relevance of results regarding the endothelial dysfunction induced by periodontopathogens that are currently obtained from 2D models. The use of in vitro 3D cellular models can also be relevant to the search for therapeutic agents for chronic inflammatory diseases such as atherosclerosis. Here, we present some strategies for the assembly of 3D cultures with endothelial cells, which is useful for the study of periodontopathogen-mediated disease., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2018
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106. A Proteomic Analysis of the Virulence Factors of Three Common Bacterial Species Involved in Periodontitis and Consequent Possible Atherosclerosis: A Narrative Review.
- Author
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Mirnejad R, Razeghian-Jahromi I, Sepehrimanesh M, Zibaeenezhad MJ, and Lopez-Jornet P
- Subjects
- Atherosclerosis complications, Atherosclerosis microbiology, Coronary Vessels metabolism, Humans, Periodontitis complications, Proteomics, Risk Factors, Atherosclerosis metabolism, Bacteria metabolism, Periodontitis microbiology, Proteome metabolism, Virulence Factors metabolism
- Abstract
The incidence of cardiovascular disorders, especially coronary artery disease and atherosclerosis, is increasing alarmingly. Clarifying the underlying causes is of the utmost importance and should be elucidated in order to reduce this growing trend. Periodontitis is known as a chronic destructive disease with sophisticated pathophysiological mechanisms that slowly impose negative effects not only on the oral tissues but also on distant organs. Additionally, it has been shown in many studies that atherosclerosis and periodontitis utilized common inflammatory signaling pathways and mediators. Several lines of evidence have demonstrated the signatures of periodontitis-related bacteria in atherosclerotic plaque specimens. It is proposed that virulent proteins of these bacteria probably accelerate the initiation or development of plaque formation on the inner walls of the coronary arteries. Proteomics techniques are very sensitive and have a global point of view. They can help to discover host factors and pathogenrelated biomarkers. This review summarizes the studies focused on the three most important bacterial species involved in both diseases and presents recent findings about the proteomic evaluation of virulence factors of these bacteria. The known mechanisms of action of the virulence factors are also described., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)
- Published
- 2018
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107. Helicobacter pylori can be related to carotid intima-media thickness, epicardial adipose tissue thickness and serum neutrophil gelatinase-associated lipocalin (NGAL) levels.
- Author
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Karadag Z, Sehitoglu T, Cure MC, Rakici H, Ayvaz MA, Bedir R, Kizilkaya B, Şahin OZ, and Cure E
- Subjects
- Adipose Tissue, Humans, Inflammation, Atherosclerosis microbiology, Carotid Intima-Media Thickness, Helicobacter Infections complications, Helicobacter pylori, Lipocalin-2 metabolism
- Abstract
Background: Helicobacter pylori (HP) affects the cardiovascular system. Our aim in this study was to evaluate, whether an infection with HP causes subclinical atherosclerosis., Methods: We included 90 patients with dyspeptic symptoms in this study. The patients underwent an upper gastrointestinal endoscopy and biopsies were taken. The patients were grouped according to histopathologic examination, as HP infection negative (n = 21), HP infection positive (+) (n = 23), HP infection (++) (n = 22), HP infection (+++), (n = 24)., Results: The neutrophilic gelatinase-associated lipocalin (NGAL) and high-sensitive C-reactive protein (hs-CRP) levels and the carotid intima-media thickness (cIMT) and epicardial adipose tissue (EAT) thickness in the HP negative group were significantly lower than the NGAL (p < 0.001) and hs-CRP (p < 0.001) levels and the cIMT (p < 0.008) and EAT (p < 0.008) thickness in the HP (+++) group. There was a strong correlation between the serum NGAL and hs-CRP levels, cIMT and EAT thickness., Conclusion: HP-infection can lead to subclinical atherosclerosis via chronic inflammation. The higher the activity of HP infection, the higher the acceleration of atherosclerosis (Tab. 3, Fig. 2, Ref. 46). Text in PDF www.elis.sk.
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- 2018
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108. Interactions of Dietary Fibre with Nutritional Components on Gut Microbial Composition, Function and Health in Monogastrics.
- Author
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Adams S, Che D, Qin G, Rui H, Sello CT, and Hailong J
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- Animals, Atherosclerosis microbiology, Atherosclerosis physiopathology, Blood Glucose metabolism, Diabetes Mellitus, Type 2 microbiology, Diabetes Mellitus, Type 2 physiopathology, Dietary Fiber administration & dosage, Fatty Acids, Volatile metabolism, Gastrointestinal Diseases microbiology, Gastrointestinal Diseases physiopathology, Gastrointestinal Tract metabolism, Gastrointestinal Transit, Humans, Insulin metabolism, Intestinal Absorption, Intestines physiology, Obesity microbiology, Obesity physiopathology, Dietary Fiber metabolism, Gastrointestinal Microbiome physiology, Nutritional Physiological Phenomena
- Abstract
The relation between dietary fibre and the well-being of human and other monogastrics has recently became a hot topic as shown by the increasing number of publications of the related research. The aim of this review is to describe - through a logical approach - the scientific suggestion linking possible benefits of dietary fibre on nutritional components and their effect on the gastrointestinal composition in relation to disease conditions in humans and animals. Dietary fibre plays a key role in: influencing blood glucose or insulin concentrations, stool bulkiness, reducing the pH within the digestive tract, synthesising volatile fatty acids (VFA), reducing intestinal transit time, stimulating growth of intestinal microbes, and constructively enhancing various blood parameters. The available literature suggests that fibre influences the bioavailability of nutrients and maintains the host's well-being by controlling disorders and disease prevalent with a Western way of living such as constipation and diarrhoea, diabetes, obesity, gastrointestinal inflammation, atherosclerosis, and colon cancer. Although there are some studies demonstrating that dietary fibre may be effective in the prevention and treatment of these disorders, the mechanisms involved are yet to be understood., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)
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- 2018
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109. Berberine treatment increases Akkermansia in the gut and improves high-fat diet-induced atherosclerosis in Apoe -/- mice.
- Author
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Zhu L, Zhang D, Zhu H, Zhu J, Weng S, Dong L, Liu T, Hu Y, and Shen X
- Subjects
- Animals, Aorta metabolism, Aorta pathology, Aortic Diseases genetics, Aortic Diseases metabolism, Aortic Diseases microbiology, Atherosclerosis genetics, Atherosclerosis metabolism, Atherosclerosis microbiology, Cytokines metabolism, Disease Models, Animal, Female, Inflammation Mediators metabolism, Intestinal Mucosa metabolism, Intestinal Mucosa microbiology, Mice, Inbred C57BL, Mice, Knockout, ApoE, Plaque, Atherosclerotic, Tight Junction Proteins metabolism, Verrucomicrobia growth & development, Verrucomicrobia metabolism, Anti-Inflammatory Agents pharmacology, Aorta drug effects, Aortic Diseases prevention & control, Atherosclerosis prevention & control, Berberine pharmacology, Diet, High-Fat, Gastrointestinal Microbiome drug effects, Intestinal Mucosa drug effects, Verrucomicrobia drug effects
- Abstract
Background and Aims: Gut microbiota plays a major role in metabolic disorders. Berberine is used to treat obesity, diabetes and atherosclerosis. The mechanism underlying the role of berberine in modulating metabolic disorders is not fully clear because berberine has poor oral bioavailability. Thus, we evaluated whether the antiatherosclerotic effect of berberine is related to alterations in gut microbial structure and if so, whether specific bacterial taxa contribute to the beneficial effects of berberine., Methods: Apoe
-/- mice were fed either a normal-chow diet or a high-fat diet (HFD). Berberine was administered to mice in drinking water (0.5 g/L) for 14 weeks. Gut microbiota profiles were established by high throughput sequencing of the V3-V4 region of the bacterial 16S ribosomal RNA gene. The effects of berberine on metabolic endotoxemia, tissue inflammation and gut barrier integrity were also investigated., Results: Berberine treatment significantly reduced atherosclerosis in HFD-fed mice. Akkermansia spp. abundance was markedly increased in HFD-fed mice treated with berberine. Moreover, berberine decreased HFD-induced metabolic endotoxemia and lowered arterial and intestinal expression of proinflammatory cytokines and chemokines. Berberine treatment increased intestinal expression of tight junction proteins and the thickness of the colonic mucus layer, which are related to restoration of gut barrier integrity in HFD-fed mice., Conclusions: Modulation of gut microbiota, specifically an increase in the abundance of Akkermansia, may contribute to the antiatherosclerotic and metabolic protective effects of berberine, which is poorly absorbed orally. Our findings therefore support the therapeutic value of gut microbiota manipulation in treating atherosclerosis., (Copyright © 2017 Elsevier B.V. All rights reserved.)- Published
- 2018
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110. Is there an Association Between Periodontitis and Atherosclerosis in Adults? A Systematic Review.
- Author
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Almeida APCPSC, Fagundes NCF, Maia LC, and Lima RR
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- Adult, Age Factors, Aged, Atherosclerosis diagnosis, Atherosclerosis immunology, Atherosclerosis microbiology, Bacteria immunology, C-Reactive Protein immunology, C-Reactive Protein metabolism, Diabetes Mellitus epidemiology, Female, Host-Pathogen Interactions, Humans, Inflammation Mediators blood, Inflammation Mediators immunology, Interleukin-6 blood, Interleukin-6 immunology, Male, Middle Aged, Periodontitis diagnosis, Periodontitis immunology, Periodontitis microbiology, Prognosis, Risk Factors, Sex Factors, Smoking adverse effects, Smoking epidemiology, Atherosclerosis epidemiology, Periodontitis epidemiology
- Abstract
Background: Atherosclerosis is a multifactorial inflammatory disease of the cardiovascular system. It has been suggested that periodontitis, an infectious disease of oral cavity caused by gramnegative anaerobic bacteria, could be linked to atherosclerosis., Objective: The objective of this systematic review was to assess the evidence between the association of periodontitis and atherosclerosis in adults., Methods: A systematic literature search was conducted in 7 databases up to January 2017, according to the Preferential Reports for Systematic Review and Meta-analysis (PRISMA) guidelines. Studies in humans with atherosclerosis were considered eligible when considering a group exposed to periodontitis and a control group (absence of periodontitis), in which the primary outcome was the association between the 2 diseases (atherosclerosis and periodontitis). The synthesis of the qualitative studies included was evaluated using previously validated checklist for assessing the risk of bias., Results: Among the 2138 studies found, 4 observational studies met the eligibility criteria and were included in the qualitative synthesis. All articles were considered adequate, presenting consistent and valid information. The results of the selected studies show the expected effects, being considered as low risk of bias., Conclusion: The available evidence indicates an association between the 2 diseases, with elevated levels of inflammatory markers, mainly C-reactive protein and interleukin 6., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)
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- 2018
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111. Atherosclerosis: Association between the gut microbiome and atherosclerosis.
- Author
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Barrington WT and Lusis AJ
- Subjects
- Humans, Atherosclerosis etiology, Atherosclerosis metabolism, Atherosclerosis microbiology, Gastrointestinal Microbiome physiology, Metagenomics methods
- Published
- 2017
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112. Infectious Agents in Atherosclerotic Cardiovascular Diseases through Oxidative Stress.
- Author
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Di Pietro M, Filardo S, Falasca F, Turriziani O, and Sessa R
- Subjects
- Atherosclerosis virology, Humans, Lipid Peroxidation, NADPH Oxidases metabolism, Prostaglandin-Endoperoxide Synthases metabolism, Atherosclerosis microbiology, Communicable Diseases metabolism, Reactive Oxygen Species metabolism
- Abstract
Accumulating evidence demonstrates that vascular oxidative stress is a critical feature of atherosclerotic process, potentially triggered by several infectious agents that are considered as risk co-factors for the atherosclerotic cardiovascular diseases (CVDs). C. pneumoniae has been shown to upregulate multiple enzymatic systems capable of producing reactive oxygen species (ROS) such as NADPH oxidase (NOX) and cyclooxygenase in vascular endothelial cells, NOX and cytochrome c oxidase in macrophages as well as nitric oxide synthase and lipoxygenase in platelets contributing to both early and late stages of atherosclerosis. P. gingivalis seems to be markedly involved in the atherosclerotic process as compared to A. actinomycetemcomitans contributing to LDL oxidation and foam cell formation. Particularly interesting is the evidence describing the NLRP3 inflammasome activation as a new molecular mechanism underlying P. gingivalis -induced oxidative stress and inflammation. Amongst viral agents, immunodeficiency virus-1 and hepatitis C virus seem to have a major role in promoting ROS production, contributing, hence, to the early stages of atherosclerosis including endothelial dysfunction and LDL oxidation. In conclusion, oxidative mechanisms activated by several infectious agents during the atherosclerotic process underlying CVDs are very complex and not well-known, remaining, thus, an attractive target for future research., Competing Interests: The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
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- 2017
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113. The gut microbiome in atherosclerotic cardiovascular disease.
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Jie Z, Xia H, Zhong SL, Feng Q, Li S, Liang S, Zhong H, Liu Z, Gao Y, Zhao H, Zhang D, Su Z, Fang Z, Lan Z, Li J, Xiao L, Li J, Li R, Li X, Li F, Ren H, Huang Y, Peng Y, Li G, Wen B, Dong B, Chen JY, Geng QS, Zhang ZW, Yang H, Wang J, Wang J, Zhang X, Madsen L, Brix S, Ning G, Xu X, Liu X, Hou Y, Jia H, He K, and Kristiansen K
- Subjects
- Case-Control Studies, Fermentation, Genome-Wide Association Study, Humans, Inflammation microbiology, Liver Cirrhosis microbiology, Metagenomics, Atherosclerosis microbiology, Gastrointestinal Microbiome drug effects, Metagenome
- Abstract
The gut microbiota has been linked to cardiovascular diseases. However, the composition and functional capacity of the gut microbiome in relation to cardiovascular diseases have not been systematically examined. Here, we perform a metagenome-wide association study on stools from 218 individuals with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls. The ACVD gut microbiome deviates from the healthy status by increased abundance of Enterobacteriaceae and Streptococcus spp. and, functionally, in the potential for metabolism or transport of several molecules important for cardiovascular health. Although drug treatment represents a confounding factor, ACVD status, and not current drug use, is the major distinguishing feature in this cohort. We identify common themes by comparison with gut microbiome data associated with other cardiometabolic diseases (obesity and type 2 diabetes), with liver cirrhosis, and rheumatoid arthritis. Our data represent a comprehensive resource for further investigations on the role of the gut microbiome in promoting or preventing ACVD as well as other related diseases.The gut microbiota may play a role in cardiovascular diseases. Here, the authors perform a metagenome-wide association study on stools from individuals with atherosclerotic cardiovascular disease and healthy controls, identifying microbial strains and functions associated with the disease.
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- 2017
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114. Deposition and hydrolysis of serine dipeptide lipids of Bacteroidetes bacteria in human arteries: relationship to atherosclerosis.
- Author
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Nemati R, Dietz C, Anstadt EJ, Cervantes J, Liu Y, Dewhirst FE, Clark RB, Finegold S, Gallagher JJ, Smith MB, Yao X, and Nichols FC
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- Atherosclerosis metabolism, Bacteroidetes physiology, Brain metabolism, Dipeptides metabolism, Humans, Hydrolysis, Lipase metabolism, Lipids blood, Atherosclerosis microbiology, Bacteroidetes metabolism, Carotid Arteries metabolism, Carotid Arteries microbiology, Dipeptides chemistry, Lipid Metabolism, Lipids chemistry, Serine chemistry
- Abstract
Multiple reaction monitoring-MS analysis of lipid extracts from human carotid endarterectomy and carotid artery samples from young individuals consistently demonstrated the presence of bacterial serine dipeptide lipid classes, including Lipid 654, an agonist for human and mouse Toll-like receptor (TLR)2, and Lipid 430, the deacylated product of Lipid 654. The relative levels of Lipid 654 and Lipid 430 were also determined in common oral and intestinal bacteria from the phylum Bacteroidetes and human serum and brain samples from healthy adults. The median Lipid 430/Lipid 654 ratio observed in carotid endarterectomy samples was significantly higher than the median ratio in lipid extracts of common oral and intestinal Bacteroidetes bacteria, and serum and brain samples from healthy subjects. More importantly, the median Lipid 430/Lipid 654 ratio was significantly elevated in carotid endarterectomies when compared with control artery samples. Our results indicate that deacylation of Lipid 654 to Lipid 430 likely occurs in diseased artery walls due to phospholipase A2 enzyme activity. These results suggest that commensal Bacteriodetes bacteria of the gut and the oral cavity may contribute to the pathogenesis of TLR2-dependent atherosclerosis through serine dipeptide lipid deposition and metabolism in artery walls., (Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.)
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- 2017
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115. Porphyromonas gingivalis Infection Accelerates Atherosclerosis Mediated by Oxidative Stress and Inflammatory Responses in ApoE-/- Mice.
- Author
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Xuan Y, Shi Q, Liu GJ, Luan QX, and Cai Y
- Subjects
- Animals, Atherosclerosis enzymology, Atherosclerosis pathology, Bacteroidaceae Infections pathology, Inflammation blood, Lipids blood, Liver metabolism, Male, Mice, Mice, Knockout, Myocardium metabolism, NF-kappa B metabolism, Nitric Oxide Synthase Type II metabolism, Oxidative Stress, Random Allocation, Sinus of Valsalva pathology, Apolipoproteins E physiology, Atherosclerosis microbiology, Bacteroidaceae Infections complications, Porphyromonas gingivalis
- Abstract
Background: The periodontal pathogen Porphyromonas gingivalis (P. gingivalis) has been proven to accelerate the development of atherosclerosis in apolipoprotein E (ApoE)-deficient mice. In this study, we used an ApoE knockout (ApoE-/-) mouse model with chronic intravenous infection with P. gingivalis to investigate the possible mechanisms of P. gingivalis-induced atherosclerosis., Methods: Eight-week-old ApoE-/- mice were randomly assigned to two groups: (a) ApoE-/- + PBS (n = 8); (b) ApoE-/- + P. gingivalis (n = 8). Both of the groups received intravenous injections 3 times per week. After 4 weeks, oxidative stress mediators in serum, heart, aorta, and liver tissues were analyzed by using histology, ELISA, realtime PCR, and Western blot., Results: Development of atherosclerosis as plaque formation in the aorta has been confirmed upon P. gingivalis infection. An abnormal lipid profile was found in the serum (increased amounts of very low-density lipoprotein [vLDL] and oxidized low-density lipoprotein [oxLDL], and decreased amount of HDL) and in some organs including heart, aorta or liver (increased mRNA levels of oxidized low-density lipoprotein receptor-1 [LOX-1] or fatty acid synthase [FAS]). Meanwhile, aggravated oxidative stress (higher level of reactive oxygen species [ROS] in the serum, and increased mRNA levels of nicotinamide adenine dinucleotide phosphate oxidase [NOX]-2 and/or NOX-4 in the three organs) was observed, as well as enhanced inflammatory responses (increased expression and secretion of C-reactive protein [CRP] in the liver and serum, and increased mRNA levels of cyclooxygenase-2 [NOX-2] and/or inducible nitric oxide synthase [iNOS] in the three organs). Besides, inflammatory mediators including nuclear factor of kappa B (NF-κB) and iNOS showed increased protein levels in the three organs after P. gingivalis infection., Conclusions: These results suggest that chronic intravenous infection with P. gingivalis in ApoE-/- mice could accelerate the development of atherosclerosis, possibly associated with mediating oxidative stress as well as inflammatory responses and disturbing the lipid profile.
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- 2017
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116. Tanshinone IIA Attenuates Atherosclerosis in Apolipoprotein E Knockout Mice Infected with Porphyromonas gingivalis.
- Author
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Xuan Y, Gao Y, Huang H, Wang X, Cai Y, and Luan QX
- Subjects
- Abietanes therapeutic use, Animals, Apolipoproteins E genetics, Atherosclerosis microbiology, Bacteroidaceae Infections, Cytokines metabolism, Down-Regulation, Mice, Mice, Knockout, MicroRNAs drug effects, Abietanes pharmacology, Atherosclerosis drug therapy, Porphyromonas gingivalis
- Abstract
Tanshinone IIA (TSA), a pharmacologically active component isolated from Danshen, may prevent cardiovascular diseases due to its anti-inflammatory, anti-oxidative, and anti-adipogenic effects. Porphyromonas gingivalis, a major periodontal pathogen, may contribute to the progression of atherosclerosis. Here, we studied the effects of TSA on atherosclerosis in ApoE
-/- mice with P. gingivalis infection. Eight-week-old ApoE-/- mice were randomized to (a) phosphate-buffered saline (PBS), (b) P. gingivalis, and (c) P. gingivalis + TSA (60 mg kg-1 day-1 ). The mice were injected with (a) PBS, or (b) and (c) P. gingivalis 3 times per week for a total of 10 times. After 8 weeks, atherosclerotic risk factors in serum and in heart, aorta, and liver tissues were analyzed in all mice using Oil Red O, atherosclerosis cytokine antibody arrays, enzyme-linked immunosorbent assay (ELISA), real-time PCR, and microRNA array. CD40, G-CSF, IFN-γ, interleukin (IL)-1β, IL-6, MCP-1, MIP-3α, tumor necrosis factor-α (TNF-α), and VEGF were attenuated by TSA in atherosclerosis cytokine antibody arrays. TSA-treated mice showed a significant reduction of C-reactive protein (CRP), ox-LDL, IL-1β, IL-6, IL-12, and TNF-α in ELISA data. Real-time PCR analyses showed that TSA decreased the expression of CCL-2, CD40, IL-1β, IL-6, TNF-α, and MMP-2 in heart and aorta tissues. Moreover, hepatic CRP was downregulated by TSA, although FASN and HMG-CoA were not. The relative expressions of miR-146b and miR-155 were elevated by P. gingivalis infection and were downregulated by TSA treatment. These results suggest that TSA was a potential therapeutic agent that may have the ability to prevent P. gingivalis-induced atherosclerosis associated with anti-inflammatory and anti-oxidative effects.- Published
- 2017
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117. Gut Microbiota and Atherosclerosis.
- Author
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Li DY and Tang WHW
- Subjects
- Animals, Bile Acids and Salts metabolism, Carnitine metabolism, Diet, Disease Models, Animal, Humans, Atherosclerosis drug therapy, Atherosclerosis metabolism, Atherosclerosis microbiology, Gastrointestinal Microbiome immunology, Methylamines metabolism
- Abstract
Purpose of Review: Studies in microbiota-mediated health risks have gained traction in recent years since the compilation of the Human Microbiome Project. No longer do we believe that our gut microbiota is an inert set of microorganisms that reside in the body without consequence. In this review, we discuss the recent findings which further our understanding of the connection between the gut microbiota and the atherosclerosis., Recent Findings: We evaluate studies which illustrate the current understanding of the relationship between infection, immunity, altered metabolism, and bacterial products such as immune activators or dietary metabolites and their contributions to the development of atherosclerosis. In particular, we critically examine rec ent clinical and mechanistic findings for the novel microbiota-dependent dietary metabolite, trimethylamine N-oxide (TMAO), which has been implicated in atherosclerosis. These discoveries are now becoming integrated with advances in microbiota profiling which enhance our ability to interrogate the functional role of the gut microbiome and develop strategies for targeted therapeutics. The gut microbiota is a multi-faceted system that is unraveling novel contributors to the development and progression of atherosclerosis. In this review, we discuss historic and novel contributors while highlighting the TMAO story mainly as an example of the various paths taken beyond deciphering microbial composition to elucidate downstream mechanisms that promote (or protect from) atherogenesis in the hopes of translating these findings from bench to bedside.
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- 2017
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118. Bacterial profile in human atherosclerotic plaques.
- Author
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Lindskog Jonsson A, Hållenius FF, Akrami R, Johansson E, Wester P, Arnerlöv C, Bäckhed F, and Bergström G
- Subjects
- Aged, Asymptomatic Diseases, Atherosclerosis pathology, Atherosclerosis surgery, Bacteria genetics, Carotid Arteries pathology, Carotid Arteries surgery, Carotid Stenosis pathology, Carotid Stenosis surgery, DNA, Bacterial genetics, Endarterectomy, Carotid, Female, Humans, Male, Middle Aged, Phylogeny, Polymerase Chain Reaction, Ribotyping, Atherosclerosis microbiology, Bacteria classification, Carotid Arteries microbiology, Carotid Stenosis microbiology, Plaque, Atherosclerotic
- Abstract
Background and Aims: Several studies have confirmed the presence of bacterial DNA in atherosclerotic plaques, but its contribution to plaque stability and vulnerability is unclear. In this study, we investigated whether the bacterial plaque-profile differed between patients that were asymptomatic or symptomatic and whether there were local differences in the microbial composition within the plaque., Methods: Plaques were removed by endarterectomy from asymptomatic and symptomatic patients and divided into three different regions known to show different histological vulnerability: A, upstream of the maximum stenosis; B, site for maximum stenosis; C, downstream of the maximum stenosis. Bacterial DNA composition in the plaques was determined by performing 454 pyrosequencing of the 16S rRNA genes, and total bacterial load was determined by qPCR., Results: We confirmed the presence of bacterial DNA in the atherosclerotic plaque by qPCR analysis of the 16S rRNA gene but observed no difference (n.s.) in the amount between either asymptomatic and symptomatic patients or different plaque regions A, B and C. Unweighted UniFrac distance metric analysis revealed no distinct clustering of samples by patient group or plaque region. Operational taxonomic units (OTUs) from 5 different phyla were identified, with the majority of the OTUs belonging to Proteobacteria (48.3%) and Actinobacteria (40.2%). There was no difference between asymptomatic and symptomatic patients, or plaque regions, when analyzing the origin of DNA at phylum, family or OTU level (n.s.)., Conclusions: There were no major differences in bacterial DNA amount or microbial composition between plaques from asymptomatic and symptomatic patients or between different plaque regions, suggesting that other factors are more important in determining plaque vulnerability., (Copyright © 2017 Elsevier B.V. All rights reserved.)
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- 2017
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119. Dietary α-cyclodextrin reduces atherosclerosis and modifies gut flora in apolipoprotein E-deficient mice.
- Author
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Sakurai T, Sakurai A, Chen Y, Vaisman BL, Amar MJ, Pryor M, Thacker SG, Zhang X, Wang X, Zhang Y, Zhu J, Yang ZH, Freeman LA, and Remaley AT
- Subjects
- Animals, Aorta drug effects, Aorta pathology, Atherosclerosis microbiology, Atherosclerosis pathology, Body Weight drug effects, Cecum drug effects, Cecum microbiology, Diet, Fat-Restricted, Diet, High-Fat adverse effects, Dietary Supplements, Female, Gastrointestinal Microbiome genetics, Intestinal Absorption, Lipids pharmacokinetics, Mice, Knockout, ApoE, alpha-Cyclodextrins metabolism, beta-Cyclodextrins metabolism, beta-Cyclodextrins pharmacology, Atherosclerosis diet therapy, Gastrointestinal Microbiome drug effects, Lipids blood, alpha-Cyclodextrins pharmacology
- Abstract
Scope: α-Cyclodextrin (α-CD), a cyclic polymer of glucose, has been shown to lower plasma cholesterol in animals and humans; however, its effect on atherosclerosis has not been previously described., Methods and Results: apoE-knockout mice were fed either low-fat diet (LFD; 5.2% fat, w/w), or Western high fat diet (21.2% fat) containing either no additions (WD), 1.5% α-CD (WDA); 1.5% β-CD (WDB); or 1.5% oligofructose-enriched inulin (WDI). Although plasma lipids were similar after 11 weeks on the WD vs. WDA diets, aortic atherosclerotic lesions were 65% less in mice on WDA compared to WD (P < 0.05), and similar to mice fed the LFD. No effect on atherosclerosis was observed for the other WD supplemented diets. By RNA-seq analysis of 16S rRNA, addition of α-CD to the WD resulted in significantly decreased cecal bacterial counts in genera Clostridium and Turicibacterium, and significantly increased Dehalobacteriaceae. At family level, Comamonadaceae significantly increased and Peptostreptococcaceae showed a negative trend. Several of these bacterial count changes correlated negatively with % atherosclerotic lesion and were associated with increased cecum weight and decreased plasma cholesterol levels., Conclusion: Addition of α-CD to the diet of apoE-knockout mice decreases atherosclerosis and is associated with changes in the gut flora., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2017
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120. Molecular characterisation of Chlamydia pneumoniae associated to atherosclerosis.
- Author
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El Yazouli L, Criscuolo A, Hejaji H, Bouazza M, Elmdaghri N, Aroussi Alami A, Amraoui A, Dakka N, and Radouani F
- Subjects
- Adult, Aged, Atherosclerosis pathology, Bacterial Typing Techniques, Base Sequence, Case-Control Studies, Chlamydophila Infections pathology, Chlamydophila pneumoniae classification, Chlamydophila pneumoniae isolation & purification, Female, Humans, Leukocytes, Mononuclear metabolism, Leukocytes, Mononuclear microbiology, Male, Middle Aged, Morocco, Plaque, Atherosclerotic pathology, Sequence Alignment, Sequence Analysis, DNA, Sequence Homology, Nucleic Acid, Atherosclerosis microbiology, Chlamydophila Infections microbiology, Chlamydophila pneumoniae genetics, DNA, Bacterial genetics, Phylogeny, Plaque, Atherosclerotic microbiology
- Abstract
Chlamydia pneumoniae is a respiratory pathogen associated with chronic inflammatory diseases such as asthma and atherosclerosis, and its detection in human carotid and coronary atheroma suggests some support for its involvement in atherogenesis. The main objective of our study was to evaluate the association between Chlamydia pneumoniae and atherosclerosis in Moroccan patients through a case-control approach and detected strain genotyping. A total of 137 cases and 124 controls were enrolled, nested PCR was performed for Chlamydia pneumoniae screening of the peripheral blood mononuclear cells (PBMCs) of both cases and controls as well as atheroma plaques from 37 cases, and positive samples were subjected to sequencing for genotyping and phylogenetic analysis. The results showed 54% and 18%, respectively, for positivity in cases and control PBMCs and 86.5% in atheroma plaques, the difference being significant between the two groups (P < 0.001, ORa = 8.580, CI, 95% [3.273-22.491]). Strain sequence analyses showed more than 98% similarity with human reference strains, and revealed various genotypes. This study supports the involvement of Chlamydia pneumoniae in atherosclerosis in the studied population and genotyping revealed that detected strains were identical to human strains circulating worldwide.
- Published
- 2017
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121. Targeting of microbe-derived metabolites to improve human health: The next frontier for drug discovery.
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Brown JM and Hazen SL
- Subjects
- Animals, Humans, Mice, Atherosclerosis drug therapy, Atherosclerosis etiology, Atherosclerosis microbiology, Drug Discovery, Gastrointestinal Microbiome, Methylamines metabolism, Methylamines toxicity
- Abstract
Recent advances in metabolomic and genome mining approaches have uncovered a poorly understood metabolome that originates solely or in part from bacterial enzyme sources. Whether living on exposed surfaces or within our intestinal tract, our microbial inhabitants produce a remarkably diverse set of natural products and small molecule metabolites that can impact human health and disease. Highlighted here, the gut microbe-derived metabolite trimethylamine N -oxide has been causally linked to the development of cardiovascular diseases. Recent studies reveal drugging this pathway can inhibit atherosclerosis development in mice. Building on this example, we discuss challenges and untapped potential of targeting bacterial enzymology for improvements in human health., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)
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- 2017
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122. Fecal microbiota transplantation in metabolic syndrome: History, present and future.
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de Groot PF, Frissen MN, de Clercq NC, and Nieuwdorp M
- Subjects
- Animals, Atherosclerosis microbiology, Atherosclerosis therapy, Clostridium Infections therapy, Disease Models, Animal, Feces microbiology, Gastrointestinal Microbiome, Humans, Inflammation therapy, Inflammatory Bowel Diseases microbiology, Inflammatory Bowel Diseases therapy, Insulin Resistance, Intestines microbiology, Metabolic Syndrome microbiology, Non-alcoholic Fatty Liver Disease microbiology, Non-alcoholic Fatty Liver Disease therapy, Randomized Controlled Trials as Topic, Fecal Microbiota Transplantation trends, Host-Pathogen Interactions, Metabolic Syndrome therapy
- Abstract
The history of fecal microbiota transplantation (FMT) dates back even to ancient China. Recently, scientific studies have been looking into FMT as a promising treatment of various diseases, while in the process teaching us about the interaction between the human host and its resident microbial communities. Current research focuses mainly on Clostridium difficile infections, however interest is rising in other areas such as inflammatory bowel disease (IBD) and the metabolic syndrome. With regard to the latter, the intestinal microbiota might be causally related to the progression of insulin resistance and diabetes. FMT in metabolic syndrome has proven to be an intriguing method to study the role of the gut microbiota and open the way to new therapies by dissecting in whom insulin resistance is driven by microbiota. In this article we review the history of FMT, the present evidence on its role in the pathophysiology of metabolic syndrome and its efficacy, limitations and future prospects.
- Published
- 2017
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123. Commensal bacteria at the crossroad between cholesterol homeostasis and chronic inflammation in atherosclerosis.
- Author
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Kasahara K, Tanoue T, Yamashita T, Yodoi K, Matsumoto T, Emoto T, Mizoguchi T, Hayashi T, Kitano N, Sasaki N, Atarashi K, Honda K, and Hirata KI
- Subjects
- Animals, Atherosclerosis genetics, Atherosclerosis metabolism, Atherosclerosis pathology, Bacteria metabolism, Bacteria pathogenicity, Cholesterol genetics, Cholesterol 7-alpha-Hydroxylase genetics, Diet, Disease Models, Animal, Fibroblast Growth Factors genetics, Gastrointestinal Microbiome genetics, Homeostasis, Humans, Ileum metabolism, Ileum microbiology, Inflammation genetics, Inflammation metabolism, Inflammation pathology, Lipid Metabolism genetics, Mice, Receptor, Fibroblast Growth Factor, Type 4 genetics, Apolipoproteins E genetics, Atherosclerosis microbiology, Cholesterol metabolism, Inflammation microbiology
- Abstract
The gut microbiota were shown to play critical roles in the development of atherosclerosis, but the detailed mechanism is limited. The purpose of this study is to clarify the influence of gut microbiota on atherogenesis via lipid metabolism and systemic inflammation. Germ-free or conventionally raised (Conv) ApoE-deficient ( ApoE
-/- ) mice were fed chow diet and euthanized at 20 weeks of age. We found that the lack of gut microbiota in ApoE-/- mice caused a significant increase in the plasma and hepatic cholesterol levels compared with Conv ApoE-/- mice. The absence of gut microbiota changed the bile acid composition in the ileum, which was associated with activation of the enterohepatic fibroblast growth factor 15, fibroblast growth factor receptor 4 axis, and reduction of cholesterol 7α-hydroxylase and hepatic bile acid synthesis, resulting in the accumulation of liver cholesterol content. However, we found that the lack of microbiota caused a significant reduction in atherosclerotic lesion formation compared with Conv ApoE-/- mice, which might be associated with the attenuation of lipopolysaccharide-mediated inflammatory responses. Our findings indicated that the gut microbiota affected both hypercholesterolemia and atherogenesis in mice., (Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.)- Published
- 2017
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124. Cholesterol crystals enhance TLR2- and TLR4-mediated pro-inflammatory cytokine responses of monocytes to the proatherogenic oral bacterium Porphyromonas gingivalis.
- Author
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Køllgaard T, Enevold C, Bendtzen K, Hansen PR, Givskov M, Holmstrup P, and Nielsen CH
- Subjects
- Animals, Atherosclerosis complications, Atherosclerosis microbiology, Cholesterol chemistry, Humans, Inflammasomes drug effects, Inflammasomes metabolism, Interleukin-1beta metabolism, Interleukin-6 metabolism, Interleukin-8 metabolism, Mice, Monocytes metabolism, Monocytes microbiology, NLR Family, Pyrin Domain-Containing 3 Protein antagonists & inhibitors, Periodontal Diseases complications, Periodontal Diseases microbiology, Plaque, Atherosclerotic metabolism, Plaque, Atherosclerotic microbiology, Porphyromonas gingivalis metabolism, Porphyromonas gingivalis pathogenicity, Staphylococcus aureus chemistry, Staphylococcus aureus pathogenicity, Toll-Like Receptor 2 administration & dosage, Toll-Like Receptor 2 agonists, Toll-Like Receptor 2 metabolism, Toll-Like Receptor 4 administration & dosage, Toll-Like Receptor 4 agonists, Toll-Like Receptor 4 metabolism, Tumor Necrosis Factor-alpha metabolism, Atherosclerosis metabolism, Cholesterol metabolism, NLR Family, Pyrin Domain-Containing 3 Protein genetics, Periodontal Diseases metabolism
- Abstract
Cholesterol deposits and pro-inflammatory cytokines play an essential role in the pathogenesis of atherosclerosis, a predominant cause of cardiovascular disease (CVD). Epidemiological evidence has linked periodontal disease (PD) with atherosclerotic CVD. Accordingly, viable periodontal pathogens, including Porphyromonas gingivalis, have been found in atherosclerotic plaques in humans and mice. We aimed to determine whether cholesterol crystals (CHCs) and oral bacteria synergize in the stimulation of human monocytes. Incubation of human monocytes with CHCs induced secretion of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, and IL-8. Moreover, CHCs markedly enhanced secretion of IL-1β by monocytes stimulated with the toll-like receptor (TLR) 4 agonist Escherichia coli lipopolysaccharide (LPS), and the TLR2 agonist Staphylococcus aureus lipoteichoic acid. Notably, CHCs also enhanced IL-1β secretion induced by P. gingivalis LPS and IL-1β secretion induced by whole P. gingivalis bacteria. This enhancement was abrogated by the NLRP3 inflammasome inhibitors Z-YVAD-FMK and glibenclamide. CHCs had no effect on cytokine production induced by P. gingivalis gingipains. Taken together, our findings support that CHCs, via stimulation of NLRP3 inflammasomes, act in synergy with the periodontal pathogen P. gingivalis to promote monocyte secretion of pro-atherogenic cytokines.
- Published
- 2017
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125. Subclinical atherosclerosis is linked to small intestinal bacterial overgrowth via vitamin K2-dependent mechanisms.
- Author
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Ponziani FR, Pompili M, Di Stasio E, Zocco MA, Gasbarrini A, and Flore R
- Subjects
- Adult, Bacterial Infections, Calcium-Binding Proteins metabolism, Cardiovascular Diseases microbiology, Carotid Intima-Media Thickness, Dietary Supplements, Enzyme-Linked Immunosorbent Assay, Extracellular Matrix Proteins metabolism, Female, Humans, Male, Middle Aged, Risk, Surveys and Questionnaires, Ultrasonography, Vascular Calcification, Vascular Stiffness, Matrix Gla Protein, Atherosclerosis microbiology, Gastrointestinal Microbiome, Intestines microbiology, Vitamin K 2 metabolism
- Abstract
Aim: To assess the rate of matrix Gla-protein carboxylation in patients with small intestinal bacterial overgrowth (SIBO) and to decipher its association with subclinical atherosclerosis., Methods: Patients with suspected SIBO who presented with a low risk for cardiovascular disease and showed no evidence of atherosclerotic plaques were included in the study. A glucose breath test was performed in order to confirm the diagnosis of SIBO and vascular assessment was carried out by ultrasound examination. Plasma levels of the inactive form of MGP (dephosphorylated-uncarboxylated matrix Gla-protein) were quantified by ELISA and vitamin K2 intake was estimated using a food frequency questionnaire., Results: Thirty-nine patients were included in the study. SIBO was confirmed in 12/39 (30.8%) patients who also presented with a higher concentration of dephosphorylated-uncarboxylated matrix Gla-protein (9.5 μg/L vs 4.2 μg/L; P = 0.004). Arterial stiffness was elevated in the SIBO group (pulse-wave velocity 10.25 m/s vs 7.68 m/s; P = 0.002) and this phenomenon was observed to correlate linearly with the levels of dephosphorylated-uncarboxylated matrix Gla-protein (β = 0.220, R
2 = 0.366, P = 0.03). Carotid intima-media thickness and arterial calcifications were not observed to be significantly elevated as compared to controls., Conclusion: SIBO is associated with reduced matrix Gla-protein activation as well as arterial stiffening. Both these observations are regarded as important indicators of subclinical atherosclerosis. Hence, screening for SIBO, intestinal decontamination and supplementation with vitamin K2 has the potential to be incorporated into clinical practice as additional preventive measures., Competing Interests: Conflict-of-interest statement: The Authors have no conflicts of interest to declare.- Published
- 2017
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126. Role of gut microbiota in atherosclerosis.
- Author
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Jonsson AL and Bäckhed F
- Subjects
- Atherosclerosis metabolism, Atherosclerosis prevention & control, Bile Acids and Salts metabolism, Diet adverse effects, Humans, Infections complications, Lipid Metabolism physiology, Lipids blood, Mouth microbiology, Atherosclerosis microbiology, Gastrointestinal Microbiome physiology
- Abstract
Infections have been linked to the development of cardiovascular disease and atherosclerosis. Findings from the past decade have identified microbial ecosystems residing in different habitats of the human body that contribute to metabolic and cardiovascular-related disorders. In this Review, we describe three pathways by which microbiota might affect atherogenesis. First, local or distant infections might cause a harmful inflammatory response that aggravates plaque development or triggers plaque rupture. Second, metabolism of cholesterol and lipids by gut microbiota can affect the development of atherosclerotic plaques. Third, diet and specific components that are metabolized by gut microbiota can have various effects on atherosclerosis; for example, dietary fibre is beneficial, whereas the bacterial metabolite trimethylamine-N-oxide is considered harmful. Although specific bacterial taxa have been associated with atherosclerosis, which is supported by increasing mechanistic evidence, several questions remain to be answered to understand fully how the microbiota contributes to atherosclerosis and cardiovascular disease. Such knowledge might pave the way for novel diagnostics and therapeutics based on microbiota.
- Published
- 2017
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127. Intestinal Immunity and Gut Microbiota in Atherogenesis.
- Author
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Yamashita T
- Subjects
- Animals, Atherosclerosis microbiology, Atherosclerosis prevention & control, Humans, Intestines microbiology, Mice, Atherosclerosis immunology, Gastrointestinal Microbiome immunology, Intestines immunology
- Abstract
Atherosclerosis is a chronic inflammatory disease. Interventions targeting the inflammatory process could provide new strategies for preventing atherosclerotic cardiovascular diseases (CVD). Previously, we have reported that oral administration of anti-CD3 antibodies, or active vitamin D
3 , reduced atherosclerosis in mice via recruiting regulatory T cells and tolerogenic dendritic cells to the gut-associated lymphoid tissues. From this, it is reasonable to propose that the intestine could be a novel therapeutic target for prevention of atherosclerotic CVD. Recently, the association between cardio-metabolic diseases and gut microbiota has attracted increased attention. Gut microbiota, reported to be highly associated with intestinal immunity and metabolism, were shown to aggravate CVD by contributing to the production of trimethylamine-N-oxide (TMAO), a pro-atherogenic compound. We have also previously investigated the relationship between patient susceptibility to coronary artery disease (CAD) and gut microbiota. We found that the order Lactobacillales was significantly increased and the phylum Bacteroidetes was decreased in CAD patients compared with control patients. In this review article, we discuss the evidence for the relationship between the gut microbiota and cardio-metabolic diseases, and consider the gut microbiota as new potential diagnostic and therapeutic tool for treating CVD.- Published
- 2017
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128. The Helicobacter cinaedi antigen CAIP participates in atherosclerotic inflammation by promoting the differentiation of macrophages in foam cells.
- Author
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D'Elios MM, Vallese F, Capitani N, Benagiano M, Bernardini ML, Rossi M, Rossi GP, Ferrari M, Baldari CT, Zanotti G, de Bernard M, and Codolo G
- Subjects
- Aged, Atherosclerosis microbiology, Cell Polarity, Chemokines metabolism, Crystallography, X-Ray, Endothelial Cells metabolism, Endothelial Cells pathology, Female, Foam Cells metabolism, Humans, Inflammation blood, Lipoproteins, LDL metabolism, MAP Kinase Signaling System, Macrophage Activation, Male, Middle Aged, Models, Molecular, Phenotype, Plaque, Atherosclerotic blood, Plaque, Atherosclerotic pathology, Receptors, G-Protein-Coupled metabolism, Recombinant Proteins metabolism, Th1 Cells immunology, p38 Mitogen-Activated Protein Kinases metabolism, Antibodies, Bacterial blood, Antigens, Bacterial immunology, Atherosclerosis blood, Atherosclerosis immunology, Cell Differentiation, Foam Cells pathology, Helicobacter immunology, Inflammation immunology
- Abstract
Recent studies have shown that certain specific microbial infections participate in atherosclerosis by inducing inflammation and immune reactions, but how the pathogens implicated in this pathology trigger the host responses remains unknown. In this study we show that Helicobacter cinaedi (Hc) is a human pathogen linked to atherosclerosis development since at least 27% of sera from atherosclerotic patients specifically recognize a protein of the Hc proteome, that we named Cinaedi Atherosclerosis Inflammatory Protein (CAIP) (n = 71). CAIP appears to be implicated in this pathology because atheromatous plaques isolated from atherosclerotic patients are enriched in CAIP-specific T cells (10%) which, in turn, we show to drive a Th1 inflammation, an immunopathological response typically associated to atherosclerosis. Recombinant CAIP promotes the differentiation and maintenance of the pro-inflammatory profile of human macrophages and triggers the formation of foam cells, which are a hallmark of atherosclerosis. This study identifies CAIP as a relevant factor in atherosclerosis inflammation linked to Hc infection and suggests that preventing and eradicating Hc infection could reduce the incidence of atherosclerosis.
- Published
- 2017
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129. Comparison of the Protective Effects of Individual Components of Particulated trans -Sialidase (PTCTS), PTC and TS, against High Cholesterol Diet-Induced Atherosclerosis in Rabbits.
- Author
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Garavelo SM, Higuchi ML, Pereira JJ, Reis MM, Kawakami JT, Ikegami RN, Palomino SA, Wadt NS, and Agouni A
- Subjects
- Animals, Aorta, Abdominal drug effects, Aorta, Abdominal pathology, Atherosclerosis metabolism, Atherosclerosis microbiology, Atherosclerosis pathology, Biological Products administration & dosage, Biological Products chemistry, Cholesterol, Dietary pharmacology, Diet, High-Fat adverse effects, Disease Models, Animal, Glycoproteins chemistry, Humans, Lipoproteins, LDL metabolism, Male, Mycoplasma pneumoniae pathogenicity, Neuraminidase chemistry, Plants, Medicinal chemistry, Plaque, Atherosclerotic microbiology, Plaque, Atherosclerotic pathology, Rabbits, Atherosclerosis drug therapy, Glycoproteins administration & dosage, Mycoplasma pneumoniae drug effects, Neuraminidase administration & dosage, Plaque, Atherosclerotic drug therapy
- Abstract
Previous studies showed the presence of Mycoplasma pneumoniae ( M. pneumoniae ) and membrane-shed microparticles (MPs) in vulnerable atherosclerotic plaques. H&S Science and Biotechnology developed PTCTS, composed by natural particles from medicinal plants (PTC) combined with trans -Sialidase (TS), to combat MPs and Mycoplasma pneumoniae . Our aim was to determine the effects of the different components of PTCTS in a rabbit model of atherosclerosis. Rabbits were fed with high cholesterol diet for 12 weeks and treated during the last 6 weeks with either vehicle, PTC, TS, or PTCTS. Lipid profile and quantification of MPs positive for Mycoplasma pneumoniae and oxidized LDL antigens were carried out. Aortas and organs were then histologically analyzed. PTCTS reduced circulating MPs positive for Mycoplasma pneumoniae and oxidized LDL antigens, reduced the plaque area in the abdominal aorta, and caused positive remodeling of the ascendant aorta. PTC caused positive remodeling and reduced plaque area in the abdominal aorta; however, TS had a lipid lowering effect. PTCTS components combined were more effective against atherosclerosis than individual components. Our data reinforce the infectious theory of atherosclerosis and underscore the potential role of circulating MPs. Therefore, the removal of Mycoplasma -derived MPs could be a new therapeutic approach in the treatment of atherosclerosis., Competing Interests: The authors declare that there are no competing interests.
- Published
- 2017
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130. Sequential colonization of periodontal pathogens in induction of periodontal disease and atherosclerosis in LDLRnull mice.
- Author
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Chukkapalli SS, Easwaran M, Rivera-Kweh MF, Velsko IM, Ambadapadi S, Dai J, Larjava H, Lucas AR, and Kesavalu L
- Subjects
- Alveolar Bone Loss etiology, Alveolar Bone Loss pathology, Animals, Antibodies, Bacterial immunology, Atherosclerosis pathology, Bacterial Infections genetics, Bacterial Infections immunology, Bacterial Infections microbiology, Bacterial Infections pathology, Dental Plaque microbiology, Dental Plaque pathology, Gingiva metabolism, Gingiva microbiology, Gingiva pathology, Lipids blood, Male, Mice, Mice, Knockout, Periodontal Diseases pathology, Plaque, Atherosclerotic metabolism, Plaque, Atherosclerotic pathology, Atherosclerosis genetics, Atherosclerosis microbiology, Host-Pathogen Interactions, Periodontal Diseases genetics, Periodontal Diseases microbiology, Receptors, LDL deficiency
- Abstract
Periodontal disease (PD) and atherosclerotic vascular disease (ASVD) are both chronic inflammatory diseases with a polymicrobial etiology and have been epidemiologically associated. The purpose is to examine whether periodontal bacteria that infect the periodontium can also infect vascular tissues and enhance pre-existing early aortic atherosclerotic lesions in LDLRnull mice. Mice were orally infected with intermediate bacterial colonizer Fusobacterium nucleatum for the first 12 weeks followed by late bacterial colonizers (Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia) for the remaining 12 weeks mimicking the human oral microbiota ecological colonization. Genomic DNA from all four bacterial was detected in gingival plaque by PCR, consistently demonstrating infection of mouse gingival surfaces. Infected mice had significant levels of IgG and IgM antibodies, alveolar bone resorption, and showed apical migration of junctional epithelium revealing the induction of PD. These results support the ability of oral bacteria to cause PD in mice. Detection of bacterial genomic DNA in systemic organs indicates hematogenous dissemination from the gingival pockets. Bacterial infection did not alter serum lipid fractions or serum amyloid A levels and did not induce aortic atherosclerotic plaque. This is the first study examining the causal role of periodontal bacteria in induction of ASVD in LDLRnull mice., (© FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2017
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131. Atherosclerosis of aberrant arteries from the left gastric artery into the right intralobar pulmonary sequestration complicated by mycobacterial epithelioid cell granuloma.
- Author
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Hashimoto H, Yanagiya M, Kusakabe M, Kurata A, Ohara S, Suzuki Y, Matsumoto J, and Horiuchi H
- Subjects
- Aged, Atherosclerosis microbiology, Bronchopulmonary Sequestration microbiology, Epithelioid Cells pathology, Granuloma microbiology, Granuloma pathology, Humans, Male, Atherosclerosis pathology, Bronchopulmonary Sequestration pathology, Mycobacterium avium-intracellulare Infection complications, Pulmonary Artery pathology
- Abstract
Vascular changes observed in intralobar pulmonary sequestration (PS) have been reported to be similar to those observed in pulmonary hypertension (PH). However, atherosclerosis in the pulmonary artery, which is one of the characteristic arterial changes of PH, has scarcely been reported in PS. Here, we report this unique manifestation in a 66-year-old man, in whom an intralobar PS fed by an aberrant artery branching from the left gastric artery had been identified 10 years earlier, and who was diagnosed with pneumonia after having symptoms of fever and cough. He was treated by lobectomy of the lower lobe of his right lung. Subsequently, a culture test of the fluid from the sequestrated lung was performed, which identified Mycobacterium avium. Subsequent pathological examination of the sequestrated lung demonstrated multiple epithelioid cell granulomas. Furthermore, atherosclerosis of the aberrant artery was also found, which may be associated with his advanced age. This is an extremely rare case of right intralobar PS supplied by aberrant artery with atherosclerosis originating from left gastric artery passing over the diaphragm., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2017
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132. The Association of Chlamydia pneumonia and Helicobacter pylori IgG Seropositivity With Omentin-1, Visfatin and Adiponectin Levels in Postmenopausal Women.
- Author
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Ranjbar R, Bolkheir A, Vahdat K, Assadi M, Darabi H, and Nabipour I
- Subjects
- Antibodies, Bacterial immunology, Atherosclerosis microbiology, C-Reactive Protein analysis, Chlamydophila Infections blood, Chlamydophila Infections complications, Chlamydophila Infections immunology, Chlamydophila pneumoniae immunology, Chronic Disease, Enzyme-Linked Immunosorbent Assay, Female, GPI-Linked Proteins blood, Healthy Volunteers, Helicobacter Infections blood, Helicobacter Infections complications, Helicobacter Infections immunology, Helicobacter pylori immunology, Humans, Immunoglobulin G blood, Immunoglobulin G immunology, Middle Aged, Prevalence, Prospective Studies, Risk Factors, Adiponectin blood, Antibodies, Bacterial blood, Cytokines blood, Lectins blood, Nicotinamide Phosphoribosyltransferase blood, Postmenopause blood
- Abstract
Some adipocytokines are cardioprotective or pro-inflammatory for cardiovascular system. Chronic infection with Chlamydia pneumoniae and Helicobacter pylori has been also considered as novel risk factors for atherosclerosis. The main aim of the current population-based study is to investigate the potential link between circulating adipocytokines and Chlamydia pneumoniae or Helicobacter pylori IgG seropositivities. A total of 250 healthy postmenopausal women who participated in a prospective cohort study were evaluated for IgG antibodies directed against C.pneumoniae and H. pylori. Omentin-1, visfatin, adiponectin, and high sensitivity C-reactive protein were measured by highly specific enzyme-linked immunosorbent assay methods. The prevalence of IgG antibodies against C. pneumoniae and H. pylori among the studied population was 20.4% (51 women) and 57.2% (143 women), respectively. There were no significant differences in adipocytokine levels between H. pylori IgG seropositive and H. pylori seronegative subjects. Similar results for visfatin and omentin-1 were found when C. pneumoniae IgG seropositive were compared with C. pneumoniae IgG seronegative subjects. However, in general linear model adjusted for age, body mass index and hs-CRP levels revealed significant difference between C. pneumoniae seropositive and C. pneumoniae seronegative subjects for circulating adiponectin. In conclusion, Chlamydia pneumoniae IgG seropositivity was associated with higher adiponectin levels in postmenopausal women. The elucidation of interaction mechanism of Chlamydia pneumoniae and a cardioprotective adipocytokine (adiponectin) will be useful in future therapeutic strategies.
- Published
- 2016
133. High fat diet induced atherosclerosis is accompanied with low colonic bacterial diversity and altered abundances that correlates with plaque size, plasma A-FABP and cholesterol: a pilot study of high fat diet and its intervention with Lactobacillus rhamnosus GG (LGG) or telmisartan in ApoE -/- mice.
- Author
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Chan YK, Brar MS, Kirjavainen PV, Chen Y, Peng J, Li D, Leung FC, and El-Nezami H
- Subjects
- Animals, Apolipoproteins E deficiency, Apolipoproteins E genetics, Atherosclerosis metabolism, Atherosclerosis microbiology, Atherosclerosis pathology, Diet, High-Fat adverse effects, Female, Humans, Mice, Mice, Inbred C57BL, Mice, Knockout, Pilot Projects, Telmisartan, Atherosclerosis drug therapy, Benzimidazoles administration & dosage, Benzoates administration & dosage, Cholesterol blood, Colon microbiology, Fatty Acid-Binding Proteins blood, Gastrointestinal Microbiome, Lacticaseibacillus rhamnosus physiology, Probiotics administration & dosage
- Abstract
Background: Atherosclerosis appears to have multifactorial causes - microbial component like lipopolysaccharides (LPS) and other pathogen associated molecular patterns may be plausible factors. The gut microbiota is an ample source of such stimulants, and its dependent metabolites and altered gut metagenome has been an established link to atherosclerosis. In this exploratory pilot study, we aimed to elucidate whether microbial intervention with probiotics L. rhamnosus GG (LGG) or pharmaceuticals telmisartan (TLM) could improve atherosclerosis in a gut microbiota associated manner., Methods: Atherosclerotic phenotype was established by 12 weeks feeding of high fat (HF) diet as opposed to normal chow diet (ND) in apolipoprotein E knockout (ApoE
-/- ) mice. LGG or TLM supplementation to HF diet was studied., Results: Both LGG and TLM significantly reduced atherosclerotic plaque size and improved various biomarkers including endotoxin to different extents. Colonial microbiota analysis revealed that TLM restored HF diet induced increase in Firmicutes/Bacteroidetes ratio and decrease in alpha diversity; and led to a more distinct microbial clustering closer to ND in PCoA plot. Eubacteria, Anaeroplasma, Roseburia, Oscillospira and Dehalobacteria appeared to be protective against atherosclerosis and showed significant negative correlation with atherosclerotic plaque size and plasma adipocyte - fatty acid binding protein (A-FABP) and cholesterol., Conclusion: LGG and TLM improved atherosclerosis with TLM having a more distinct alteration in the colonic gut microbiota. Altered bacteria genera and reduced alpha diversity had significant correlations to atherosclerotic plaque size, plasma A-FABP and cholesterol. Future studies on such bacterial functional influence in lipid metabolism will be warranted.- Published
- 2016
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134. Characterization of Innate Immune Responses of Human Endothelial Cells Induced by Porphyromonas gingivalis and Their Derived Outer Membrane Vesicles.
- Author
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Ho MH, Guo ZM, Chunga J, Goodwin JS, and Xie H
- Subjects
- Bacterial Outer Membrane Proteins metabolism, Blood Vessels, Cell Adhesion, Cells, Cultured, Chemokine CXCL1 biosynthesis, Chemokine CXCL1 genetics, Chemokine CXCL2 biosynthesis, Chemokine CXCL2 genetics, E-Selectin biosynthesis, E-Selectin genetics, Gene Expression Regulation, Host-Pathogen Interactions, Human Umbilical Vein Endothelial Cells microbiology, Humans, Interleukin-8 biosynthesis, Interleukin-8 genetics, Monocytes metabolism, Porphyromonas gingivalis pathogenicity, Up-Regulation, Atherosclerosis immunology, Atherosclerosis microbiology, Endothelial Cells immunology, Endothelial Cells metabolism, Immunity, Innate, Porphyromonas gingivalis immunology
- Abstract
Atherosclerosis, a chronic inflammatory disease of the blood vessels, is one of the most common causes of morbidity and mortality world-wide. Involvement of Porphyromonas gingivalis in atherosclerosis is supported by observations from epidemiological, clinical, immunological, and molecular studies. Previously we reported that P. gingivalis vesicles have a much higher invasive efficiency than their originating cells. Here, we further compare the role of P. gingivalis cells and their vesicles in expression of chemoattractant proteins including CXCL1, CXCL2, and CXCL8, and adhesive molecules such as E-selectin in human umbilical vein endothelial cells (HUVECs). Both P. gingivalis 33277 cells and vesicles were able to up-regulate expression of these molecules, while the vesicles acted as more potent inducers of the inflammatory response associated with the development of atherosclerosis, consequently resulting in significant monocyte adhesion to a monolayer of HUVECs. Interestingly, we found that elevated expression of CXCL8 and E-selectin in endothelial cells induced by P. gingivalis correlated with the invasive ability of P. gingivalis cells and vesicles. Non-invasive bacterial cells and vesicles had no effect on expression of these genes. This study highlights the potential risk of P. gingivalis cells and vesicles in initiation of atherosclerosis and provides a potential target for the development of novel therapeutics against bacteria-associated atherosclerosis.
- Published
- 2016
- Full Text
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135. Bacterial Communities Associated with Atherosclerotic Plaques from Russian Individuals with Atherosclerosis.
- Author
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Ziganshina EE, Sharifullina DM, Lozhkin AP, Khayrullin RN, Ignatyev IM, and Ziganshin AM
- Subjects
- Aged, Atherosclerosis pathology, Bacteria classification, Bacteria isolation & purification, Female, Humans, Male, Middle Aged, Principal Component Analysis, RNA, Ribosomal, 16S chemistry, RNA, Ribosomal, 16S isolation & purification, Russia, Sequence Analysis, DNA, Atherosclerosis microbiology, Bacteria genetics, Plaque, Atherosclerotic microbiology, RNA, Ribosomal, 16S metabolism
- Abstract
Atherosclerosis is considered a chronic disease of the arterial wall and is the major cause of severe disease and death among individuals all over the world. Some recent studies have established the presence of bacteria in atherosclerotic plaque samples and suggested their possible contribution to the development of cardiovascular disease. The main objective of this preliminary pilot study was to better understand the bacterial diversity and abundance in human atherosclerotic plaques derived from common carotid arteries of individuals with atherosclerosis (Russian nationwide group) and contribute towards the further identification of a main group of atherosclerotic plaque bacteria by 454 pyrosequencing their 16S ribosomal RNA (16S rRNA) genes. The applied approach enabled the detection of bacterial DNA in all atherosclerotic plaques. We found that distinct members of the order Burkholderiales were present at high levels in all atherosclerotic plaques obtained from patients with atherosclerosis with the genus Curvibacter being predominant in all plaque samples. Moreover, unclassified Burkholderiales as well as members of the genera Propionibacterium and Ralstonia were typically the most significant taxa for all atherosclerotic plaques. Other genera such as Burkholderia, Corynebacterium and Sediminibacterium as well as unclassified Comamonadaceae, Oxalobacteraceae, Rhodospirillaceae, Bradyrhizobiaceae and Burkholderiaceae were always found but at low relative abundances of the total 16S rRNA gene population derived from all samples. Also, we found that some bacteria found in plaque samples correlated with some clinical parameters, including total cholesterol, alanine aminotransferase and fibrinogen levels. Finally, our study indicates that some bacterial agents at least partially may be involved in affecting the development of cardiovascular disease through different mechanisms., Competing Interests: The authors have declared that no competing interests exist.
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- 2016
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136. [The microbiota of intestine. The role in development of various pathologies].
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Kuznetsova EE, Gorokhova VG, and Bogorodskaya SL
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- Atherosclerosis epidemiology, Atherosclerosis microbiology, Atherosclerosis pathology, Bacteroidetes pathogenicity, Diabetes Mellitus, Type 2 metabolism, Diabetes Mellitus, Type 2 microbiology, Diabetes Mellitus, Type 2 pathology, Humans, Inflammatory Bowel Diseases epidemiology, Inflammatory Bowel Diseases microbiology, Inflammatory Bowel Diseases pathology, Intestines microbiology, Metabolic Syndrome metabolism, Metabolic Syndrome microbiology, Metabolic Syndrome pathology, Obesity metabolism, Obesity microbiology, Obesity pathology, Prevotella pathogenicity, Ruminococcus pathogenicity, Bacteroidetes metabolism, Gastrointestinal Microbiome, Intestinal Mucosa metabolism, Prevotella metabolism, Ruminococcus metabolism
- Published
- 2016
137. Bacteria of leg atheromatous arteries responsible for inflammation.
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Olszewski WL, Rutkowska J, Moscicka-Wesolowska M, Swoboda-Kopec E, Stelmach E, Zaleska M, and Zagozda M
- Subjects
- Aged, Amputation, Surgical, Animals, Atherosclerosis diagnosis, Atherosclerosis metabolism, Atherosclerosis surgery, Bacteria classification, Carotid Arteries microbiology, Carotid Arteries transplantation, Cytokines metabolism, Female, Heterografts, Humans, Inflammation diagnosis, Inflammation metabolism, Inflammation Mediators metabolism, Macrophages metabolism, Macrophages microbiology, Male, Mice, SCID, Middle Aged, Popliteal Artery metabolism, Popliteal Artery pathology, Popliteal Artery transplantation, Ribotyping, Atherosclerosis microbiology, Bacteria genetics, DNA, Bacterial genetics, Inflammation microbiology, Lower Extremity blood supply, Plaque, Atherosclerotic, Popliteal Artery microbiology, RNA, Ribosomal, 16S genetics
- Abstract
Background: Ischaemia of the lower limbs is frequently followed by inflammation and, in advanced cases, necrosis of peripheral tissues. Whether this is caused by arterial hypoperfusion only or by the presence of bacteria in the arterial walI as well remains unclear. The aim of the study was to prove the presence and source of bacteria in arterial specimens and evaluate their chemotactic properties resulting in the formation of periarterial cellular infiltrates., Materials and Methods: Bacterial culture and testing for 16sRNA were performed in fragments of popliteal artery harvested from amputated limbs. Carotid artery plaques served as controls. Fragments of arteries were transplanted into scid mice to evaluate their chemotactic activity for macrophages., Results: a) higher prevalence of isolates and 16sRNA in atherosclerotic popliteal than carotid arteries, b) high density of plaque and periarterial infiltrates and mRNA level for pro-inflammatory cytokines in popliteal arteries, c) prevalent microbes were Staphylococcus aureus, S. epidermidis and Enterococci, d) foot skin and arterial bacterial phenotypes and DNA revealed evident similarities, and e) more intensive mouse macrophage accumulation in popliteal than carotid implants into scid mice., Conclusions: The presence of bacteria in the lower limb arterial wall was documented. They may predispose to inflammation secondary to ischaemic changes.
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- 2016
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138. Human β-defensin-3 alleviates the progression of atherosclerosis accelerated by Porphyromonas gingivalis lipopolysaccharide.
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Li L, Bian T, Lyu J, Cui D, Lei L, and Yan F
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- Animals, Aorta pathology, Apolipoproteins genetics, Atherosclerosis microbiology, Cytokines genetics, Cytokines metabolism, Disease Progression, Endothelial Cells immunology, Human Umbilical Vein Endothelial Cells, Humans, Inflammation Mediators metabolism, Lipopolysaccharides immunology, Lipopolysaccharides metabolism, Macrophages immunology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Signal Transduction drug effects, Anti-Infective Agents therapeutic use, Aorta drug effects, Atherosclerosis drug therapy, Endothelial Cells drug effects, Macrophages drug effects, Porphyromonas gingivalis immunology, beta-Defensins therapeutic use
- Abstract
Background and Aim: Porphyromonas gingivalis (P.gingivalis) lipopolysaccharide (LPS) is reported to be associated with the progression of atherosclerosis (AS). In this study, we explored the potential of human β-defensin-3 (hBD3), an antimicrobial peptide with immunomodulatory properties, to alleviate AS progression accelerated by P.gingivalis LPS and the mechanism underlying this effect., Materials and Methods: Apolipoprotein E-deficient mice were injected intraperitoneally with hBD3, P.gingivalis LPS, or hBD3+P.gingivalis LPS. The aorta was assessed immunohistologically and mRNA levels of inflammatory cytokines were determined by quantitative PCR. Macrophages and vascular endothelial cells were stimulated in vitro to investigate the hBD3 target cells. Inflammatory cytokines in serum and cell culture supernatants were detected using cytometric bead arrays. Signaling pathways were investigated by Western blotting., Results: In P.gingivalis LPS-treated mice, hBD3 significantly reduced serum IL-6 and TNF-α levels and aortic expression of ICAM-1, IL-6, and MCP-1 (mRNA and protein). The area and severity of atherosclerotic lesions were also diminished, with less advanced plaque formation, more continuous and distinct elastic lamina, and more normal smooth muscle cells arranged along the tunica media layer. In vitro, hBD3 decreased TNF-α, IL-1β, IL-6 secretion and downregulated TNF-α, IL-1β, IL-6, IL-8, VCAM-1, and IL-10 mRNA levels in macrophages. hBD3 did not influence TNF-α, IL-6, and IL-8 levels in HUVECs culture supernatants. Furthermore, hBD3 suppressed P.gingivalis LPS-induced activation of the NF-κB, p38 and JNK pathways., Conclusion: hBD3 alleviates AS progression accelerated by P.gingivalis LPS in apolipoprotein E-deficient mice by downregulating the cytokine expression in macrophages via the MAPK and NF-κB signaling pathways., (Copyright © 2016 Elsevier B.V. All rights reserved.)
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- 2016
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139. MixMC: A Multivariate Statistical Framework to Gain Insight into Microbial Communities.
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Lê Cao KA, Costello ME, Lakis VA, Bartolo F, Chua XY, Brazeilles R, and Rondeau P
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- Atherosclerosis genetics, Healthy Volunteers, Humans, RNA, Ribosomal, 16S genetics, Algorithms, Atherosclerosis microbiology, Bacteria genetics, Computational Biology methods, Metagenomics methods, Microbiota genetics, Models, Statistical
- Abstract
Culture independent techniques, such as shotgun metagenomics and 16S rRNA amplicon sequencing have dramatically changed the way we can examine microbial communities. Recently, changes in microbial community structure and dynamics have been associated with a growing list of human diseases. The identification and comparison of bacteria driving those changes requires the development of sound statistical tools, especially if microbial biomarkers are to be used in a clinical setting. We present mixMC, a novel multivariate data analysis framework for metagenomic biomarker discovery. mixMC accounts for the compositional nature of 16S data and enables detection of subtle differences when high inter-subject variability is present due to microbial sampling performed repeatedly on the same subjects, but in multiple habitats. Through data dimension reduction the multivariate methods provide insightful graphical visualisations to characterise each type of environment in a detailed manner. We applied mixMC to 16S microbiome studies focusing on multiple body sites in healthy individuals, compared our results with existing statistical tools and illustrated added value of using multivariate methodologies to fully characterise and compare microbial communities.
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- 2016
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140. Human β-defensin 3 suppresses Porphyromonas gingivalis lipopolysaccharide-induced inflammation in RAW 264.7 cells and aortas of ApoE-deficient mice.
- Author
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Bian T, Li L, Lyu J, Cui D, Lei L, and Yan F
- Subjects
- Animals, Apolipoproteins E genetics, Atherosclerosis blood, Atherosclerosis chemically induced, Atherosclerosis microbiology, Chemokine CCL2 blood, Humans, Inflammation blood, Inflammation chemically induced, Intercellular Adhesion Molecule-1 blood, Interleukin-6 genetics, Lipopolysaccharides chemistry, Lipopolysaccharides toxicity, Mice, Mitogen-Activated Protein Kinase Kinases drug effects, Mitogen-Activated Protein Kinase Kinases genetics, Porphyromonas gingivalis chemistry, Porphyromonas gingivalis pathogenicity, Tumor Necrosis Factor-alpha genetics, beta-Defensins metabolism, Atherosclerosis drug therapy, Inflammation drug therapy, beta-Defensins administration & dosage
- Abstract
Human beta-defensin 3 (hBD3) is an antimicrobial peptide showing immunomodulatory effect on both innate and acquired immune response. Atherosclerosis is an inflammatory disease characterized by accumulation of lipids in the vascular wall. In this study, we evaluated whether hBD3 could attenuate the atherosclerosis development accelerated by Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) with apolipoprotein E-deficient (ApoE(-/-)) mice. We observed that, in vivo, hBD3 inhibited serum MCP-1, sICAM-1 levels of ApoE-deficient mice exposed to Pg-LPS in a chronic inflammation model. Serum levels of total cholesterol (TC) and low-density lipoprotein (LDL) were also markedly reduced with hBD3 intervention. In addition, thinned vascular walls, less macrophage infiltration and the formation of atherosclerotic lesions were observed in the hBD3-treated group. Furthermore, in vitro, hBD3 profoundly suppressed the production of TNF-α and IL-6 in RAW 264.7 cells induced by Pg-LPS in a dose-dependent manner. Moreover, hBD3 attenuated the phosphorylation of p38 and ERK1/2 in the mitogen-activated protein kinase (MAPK) pathway. Taken together, our work has revealed that hBD3 exhibits potent anti-inflammatory properties both in vitro and in vivo, and this effect might be correlated with inhibition of MAPK pathway., (Copyright © 2016 Elsevier Inc. All rights reserved.)
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- 2016
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141. Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe-/- Mice.
- Author
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Li J, Lin S, Vanhoutte PM, Woo CW, and Xu A
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- Animals, Atherosclerosis microbiology, Atherosclerosis pathology, Caco-2 Cells, Disease Models, Animal, Endotoxemia etiology, Endotoxemia microbiology, Humans, Inflammation etiology, Inflammation microbiology, Male, Mice, Mice, Transgenic, Treatment Outcome, Atherosclerosis prevention & control, Endotoxemia prevention & control, Inflammation prevention & control, Intestines microbiology, Verrucomicrobia physiology
- Abstract
Background: Altered composition of the gut microbiota is involved in both the onset and progression of obesity and diabetes mellitus. However, the link between gut microbiota and obesity-related cardiovascular complications has not been explored. The present study was designed to investigate the role of Akkermansia muciniphila, a mucin-degrading bacterium with beneficial effects on metabolism, in the pathogenesis of atherosclerosis in apolipoprotein E-deficient (Apoe(-/-)) mice., Methods and Results: Apoe(-/-) mice on normal chow diet or a Western diet were treated with A muciniphila by daily oral gavage for 8 weeks, followed by histological evaluations of atherosclerotic lesion in aorta. Real-time polymerase chain reaction analysis demonstrated that the fecal abundance of A muciniphila was significantly reduced by Western diet. Replenishment with A muciniphila reversed Western diet-induced exacerbation of atherosclerotic lesion formation without affecting hypercholesterolemia. A muciniphila prevented Western diet-induced inflammation in both the circulation and local atherosclerotic lesion, as evidenced by reduced macrophage infiltration and expression of proinflammatory cytokines and chemokines. These changes were accompanied by a marked attenuation in metabolic endotoxemia. A muciniphila-mediated reduction in circulating endotoxin level could be attributed to the induction of intestinal expression of the tight junction proteins (zona occuldens protein-1 and occludin), thereby reversing Western diet-induced increases in gut permeability. Long-term infusion of endotoxin to Apoe(-/-) mice reversed the protective effect of A muciniphila against atherosclerosis., Conclusion: A muciniphila attenuates atherosclerotic lesions by ameliorating metabolic endotoxemia-induced inflammation through restoration of the gut barrier., (© 2016 American Heart Association, Inc.)
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- 2016
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142. Lack of strong association of Chlamydia pneumoniae and atherosclerosis in a Jordanian population.
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Al-Younes HM, Abu Abeeleh MA, and Jaber BM
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- Adult, Aged, Aged, 80 and over, Chlamydophila Infections microbiology, DNA, Bacterial blood, Female, Fluorescent Antibody Technique, Humans, Immunoglobulin G blood, Jordan epidemiology, Male, Middle Aged, Polymerase Chain Reaction, Prevalence, Antibodies, Bacterial blood, Atherosclerosis epidemiology, Atherosclerosis microbiology, Chlamydophila Infections complications, Chlamydophila Infections epidemiology, Chlamydophila pneumoniae immunology
- Abstract
Introduction: The correlation of Chlamydia pneumoniae to coronary artery disease (CAD) in Jordan was investigated in this study., Methodology: Totals of 361 atherosclerotic patients and 392 apparently healthy controls of both sexes were enrolled. C. pneumoniae-specific IgG antibodies were measured by the microimmunofluorescence assay (MIF). The presence of the bacterial DNA in the blood by polymerase chain reaction (PCR) was also tested., Results: The overall IgG seroprevalence, estimated at a titer of 1/16, was insignificantly higher in patients (75.9%) than in controls (71.7%). About 59.3% of patients demonstrated seropositivity at titers ≤ 1/256, which are suggestive of chronic or presumed past infection, whereas 54.1% of controls were seropositive at these titers (p > 0.05). Analysis of gender-specific seroprevalences revealed no obvious relation between C. pneumoniae and atherosclerosis in males (78.9% and 77.9% in atherosclerotic and control males, respectively; p > 0.05). However, a significantly elevated seropositivity was detected in atherosclerotic females (71.7%) compared with control females (64.2%). On the other hand, the PCR-based detection of C. pneumoniae DNA failed to correlate the bacterium to atherosclerosis., Conclusions: We were unable to show a strong association between C. pneumoniae and CAD, potentially because of the presence of high seroprevalence of C. pneumoniae antibodies and the unreliability of the whole blood-based nested PCR technique used.
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- 2016
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143. Resveratrol Attenuates Trimethylamine-N-Oxide (TMAO)-Induced Atherosclerosis by Regulating TMAO Synthesis and Bile Acid Metabolism via Remodeling of the Gut Microbiota.
- Author
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Chen ML, Yi L, Zhang Y, Zhou X, Ran L, Yang J, Zhu JD, Zhang QY, and Mi MT
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- Animals, Atherosclerosis enzymology, Atherosclerosis metabolism, Bacteria classification, Bacteria isolation & purification, Cholesterol 7-alpha-Hydroxylase genetics, Cholesterol 7-alpha-Hydroxylase metabolism, Female, Humans, Liver metabolism, Methylamines adverse effects, Mice, Mice, Inbred C57BL, Resveratrol, Atherosclerosis drug therapy, Atherosclerosis microbiology, Bacteria metabolism, Bile Acids and Salts metabolism, Gastrointestinal Microbiome, Methylamines metabolism, Stilbenes administration & dosage
- Abstract
Unlabelled: The gut microbiota is found to be strongly associated with atherosclerosis (AS). Resveratrol (RSV) is a natural phytoalexin with anti-AS effects; however, its mechanisms of action remain unclear. Therefore, we sought to determine whether the anti-AS effects of RSV were related to changes in the gut microbiota. We found that RSV attenuated trimethylamine-N-oxide (TMAO)-induced AS in ApoE(-/-) mice. Meanwhile, RSV decreased TMAO levels by inhibiting commensal microbial trimethylamine (TMA) production via gut microbiota remodeling in mice. Moreover, RSV increased levels of the genera Lactobacillus and Bifidobacterium, which increased the bile salt hydrolase activity, thereby enhancing bile acid (BA) deconjugation and fecal excretion in C57BL/6J and ApoE(-/-) mice. This was associated with a decrease in ileal BA content, repression of the enterohepatic farnesoid X receptor (FXR)-fibroblast growth factor 15 (FGF15) axis, and increased cholesterol 7a-hydroxylase (CYP7A1) expression and hepatic BA neosynthesis. An FXR antagonist had the same effect on FGF15 and CYP7A1 expression as RSV, while an FXR agonist abolished RSV-induced alterations in FGF15 and CYP7A1 expression. In mice treated with antibiotics, RSV neither decreased TMAO levels nor increased hepatic BA synthesis. Additionally, RSV-induced inhibition of TMAO-caused AS was also markedly abolished by antibiotics. In conclusion, RSV attenuated TMAO-induced AS by decreasing TMAO levels and increasing hepatic BA neosynthesis via gut microbiota remodeling, and the BA neosynthesis was partially mediated through the enterohepatic FXR-FGF15 axis., Importance: Recently, trimethylamine-N-oxide (TMAO) has been identified as a novel and independent risk factor for promoting atherosclerosis (AS) partially through inhibiting hepatic bile acid (BA) synthesis. The gut microbiota plays a key role in the pathophysiology of TMAO-induced AS. Resveratrol (RSV) is a natural phytoalexin with prebiotic benefits. A growing body of evidence supports the hypothesis that phenolic phytochemicals with poor bioavailability are possibly acting primarily through remodeling of the gut microbiota. The current study showed that RSV attenuated TMAO-induced AS by decreasing TMAO levels and increasing hepatic BA neosynthesis via gut microbiota remodeling. And RSV-induced hepatic BA neosynthesis was partially mediated through downregulating the enterohepatic farnesoid X receptor-fibroblast growth factor 15 axis. These results offer new insights into the mechanisms responsible for RSV's anti-AS effects and indicate that the gut microbiota may become an interesting target for pharmacological or dietary interventions to decrease the risk of developing cardiovascular diseases., (Copyright © 2016 Chen et al.)
- Published
- 2016
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144. Trimethylamine-N-oxide: a link between the gut microbiome, bile acid metabolism, and atherosclerosis.
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Wilson A, McLean C, and Kim RB
- Subjects
- Animals, Atherosclerosis microbiology, Firmicutes physiology, Humans, Oxygenases metabolism, Atherosclerosis metabolism, Bile Acids and Salts metabolism, Gastrointestinal Microbiome, Methylamines metabolism
- Abstract
Purpose of Review: This article evaluates the link between trimethylamine-N-oxide (TMAO) and bile acids and the consequent impact on the development of atherosclerosis., Recent Findings: Elevation in plasma TMAO concentrations is associated with an increased risk of cardiovascular disease in many different patient cohorts. In addition to the recently identified direct effects of TMAO on the development of atherosclerosis, other components involved in TMAO metabolism may also have an impact. Furthermore, the relationship between TMAO and bile acid regulation is emerging as a possible mediator of atherosclerosis., Summary: Studies that are emerging highlight the mechanistic relationship of TMAO to the development atherosclerosis in addition to its role as disease biomarker. The interplay between TMAO and bile acid metabolism mediated through multiple factors, such as the gut microbiome, farnesoid X receptor signaling, and flavin monooxygenase 3 activity may help identify another pathway by which atherosclerosis occurs. In this review, we discuss the most recent data regarding atherosclerosis, TMAO, and bile acid metabolism.
- Published
- 2016
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145. The role of intestinal microbiota in the pathogenesis of metabolic diseases.
- Author
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Węgielska I and Suliburska J
- Subjects
- Atherosclerosis microbiology, Atherosclerosis prevention & control, Diabetes Mellitus, Type 2 microbiology, Diabetes Mellitus, Type 2 prevention & control, Energy Intake, Humans, Intestinal Mucosa metabolism, Intestines microbiology, Metabolic Diseases prevention & control, Obesity microbiology, Obesity prevention & control, Postnatal Care, Prebiotics, Prenatal Care, Probiotics, Gastrointestinal Microbiome, Metabolic Diseases microbiology
- Abstract
The incidence of metabolic diseases is increasing rapidly all over the world. This situation has led researchers to attempt to explain the pathomechanisms of these disorders and to develop specific recommendations for the prevention and treatment of diseases such as obesity, type-2 diabetes, and atherosclerosis. Recent studies show clear evidence of the role of human intestinal microbiota in health and in predispositions to diseases. Gut microbiota affect a number of complex metabolic reactions, significantly altering the functioning of the human body. Numerous experiments have shown the key role played by the formation process of the intestinal ecosystem in the early stages of human life for programming its metabolic health. The following article is a compilation of the literature available on the formation of the complex intestinal ecosystem and its impact on the incidence of diseases such as obesity, type-2 diabetes, and atherosclerosis.
- Published
- 2016
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146. Tolerization against atherosclerosis using heat shock protein 60.
- Author
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Wick C
- Subjects
- Animals, Atherosclerosis pathology, Atherosclerosis prevention & control, Bacteria immunology, Bacterial Infections complications, Bacterial Infections immunology, Bacterial Infections microbiology, Bacterial Proteins immunology, Cytokines immunology, Endothelium, Vascular immunology, Endothelium, Vascular microbiology, Endothelium, Vascular pathology, Humans, Immune Tolerance, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory microbiology, T-Lymphocytes, Regulatory pathology, Atherosclerosis immunology, Atherosclerosis microbiology, Autoimmunity, Chaperonin 60 immunology
- Abstract
Atherosclerosis is a chronic inflammatory disease of the artery wall, and both innate and adaptive immunity play important roles in the pathogenesis of this disease. In several experimental and human experiments of early atherosclerotic lesions, it has been shown that the first pathogenic event in atherogenesis is intimal infiltration of T cells at predilection sites. These T cells react to heat shock protein 60 (HSP60), which is a ubiquitous self-antigen expressed on the surface of endothelial cells (ECs) together with adhesion molecules in response to classical risk factors for atherosclerosis. When HSP60 is expressed on the EC surface, it can act as a "danger-signal" for both cellular and humoral immune reactions. Acquired by infection or vaccination, beneficial protective immunity to microbial HSP60 and bona fide autoimmunity to biochemically altered autologous HSP60 is present in all humans. Thus, the development of atherosclerosis during aging is paid by the price for lifelong protective preexisting anti-HSP60 immunity by harmful (auto)immune cross-reactive attack on arterial ECs maltreated by atherosclerosis risk factors. This is supported by experiments, which shows that bacterial HSP60 immunization can lead and accelerate experimental atherosclerosis. This review article presents accumulating proof that supports the idea that tolerization with antigenic HSP60 protein or its peptides may arrest or even prevent atherosclerosis by increased production of regulatory T cells and/or anti-inflammatory cytokines. Recent data indicates that HSP60, or more likely some of its derivative peptides, has immunoregulatory functions. Therefore, these peptides may have important potential for being used as diagnostic agents or therapeutic targets.
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- 2016
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147. The presence of biofilm structures in atherosclerotic plaques of arteries from legs amputated as a complication of diabetic foot ulcers.
- Author
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Snow DE, Everett J, Mayer G, Cox SB, Miller B, Rumbaugh K, Wolcott RA, and Wolcott RD
- Subjects
- Adult, Aged, Amputation, Surgical, Arteries ultrastructure, Humans, Male, Middle Aged, Risk Factors, Atherosclerosis etiology, Atherosclerosis microbiology, Biofilms, Diabetic Foot complications, Inflammation etiology, Inflammation microbiology, Plaque, Atherosclerotic microbiology
- Abstract
Objective: Atherosclerosis, rather than microcirculatory impairment caused by endothelial cell dysfunction, is the main driver of circulatory compromise in patients with diabetic limbs. The presence of atherosclerotic plaque at the trifurcation is a significant contributor to amputation of diabetic legs. The presence of bacteria and other microorganisms in atherosclerotic plaque has long been known, however, the cause of chronic inflammation and the role of bacteria/viruses in atherosclerosis have not been studied in detail. The objective of this study was to clarify the cause of the chronic inflammation within atherosclerotic plaques, and determine if any bacteria and/or viruses are involved in the inflammatory pathway., Method: This study uses fluorescence microscopy and fluorescence in-situ hybridisation (FISH) to identify components of biofilm in atherosclerotic arteries. These tools are also used to identify individual bacteria, and determine the architectural spatial location within the atherosclerotic plaque where the bacteria can be found., Results: The results indicate that the presence of biofilms in grossly involved arteries may be an important factor in chronic inflammatory pathways of atherosclerotic progression, in the amputated limbs of patients with diabetic foot ulcers and vascular disease., Conclusion: While the presence of bacterial biofilm structures in atherosclerotic plaque does not prove that biofilm is the proximate cause of atherosclerosis, it could contribute to the persistent inflammation associated with it. Second, the synergistic relationship between the atherosclerotic infection and the diabetic foot ulcer may ultimately contribute to higher amputation rates in diabetics., Declaration of Interest: RAW and RDW have equity interest in PathoGenius, a clinical laboratory using DNA to identify microbes.
- Published
- 2016
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148. Comparative genomic analysis of human Chlamydia pneumoniae isolates from respiratory, brain and cardiac tissues.
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Roulis E, Bachmann NL, Myers GS, Huston W, Summersgill J, Hudson A, Dreses-Werringloer U, Polkinghorne A, and Timms P
- Subjects
- Adaptation, Physiological genetics, Alzheimer Disease microbiology, Atherosclerosis microbiology, Brain microbiology, Chlamydophila Infections microbiology, Chlamydophila pneumoniae classification, Chlamydophila pneumoniae physiology, Evolution, Molecular, Heart microbiology, Host-Pathogen Interactions, Humans, Mutation, Phylogeny, Polymorphism, Single Nucleotide, Recombination, Genetic, Respiratory System microbiology, Species Specificity, Chlamydophila pneumoniae genetics, Genome, Bacterial genetics, Genomics methods, Sequence Analysis, DNA methods
- Abstract
Chlamydia pneumoniae is an obligate intracellular bacterium implicated in a wide range of human diseases including atherosclerosis and Alzheimer's disease. Efforts to understand the relationships between C. pneumoniae detected in these diseases have been hindered by the availability of sequence data for non-respiratory strains. In this study, we sequenced the whole genomes for C. pneumoniae isolates from atherosclerosis and Alzheimer's disease, and compared these to previously published C. pneumoniae genomes. Phylogenetic analyses of these new C. pneumoniae strains indicate two sub-groups within human C. pneumoniae, and suggest that both recombination and mutation events have driven the evolution of human C. pneumoniae. Further fine-detailed analyses of these new C. pneumoniae sequences show several genetically variable loci. This suggests that similar strains of C. pneumoniae are found in the brain, lungs and cardiovascular system and that only minor genetic differences may contribute to the adaptation of particular strains in human disease., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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149. Periodontal pathogens invade gingiva and aortic adventitia and elicit inflammasome activation in αvβ6 integrin-deficient mice.
- Author
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Velsko IM, Chukkapalli SS, Rivera-Kweh MF, Zheng D, Aukhil I, Lucas AR, Larjava H, and Kesavalu L
- Subjects
- Adventitia immunology, Adventitia microbiology, Animals, Antigens, Neoplasm genetics, Aorta immunology, Aorta microbiology, Atherosclerosis immunology, Atherosclerosis microbiology, Atherosclerosis pathology, Bacteroidetes growth & development, Bacteroidetes immunology, Bacteroidetes pathogenicity, Bone Resorption, Disease Models, Animal, Fusobacterium nucleatum growth & development, Fusobacterium nucleatum immunology, Fusobacterium nucleatum pathogenicity, Gene Expression, Gingiva immunology, Gingiva microbiology, Gingiva pathology, In Situ Hybridization, Fluorescence, Inflammasomes, Integrins deficiency, Integrins genetics, Lipoproteins, LDL genetics, Lipoproteins, LDL immunology, Mice, Mice, Knockout, Microbial Consortia, Periodontitis immunology, Periodontitis microbiology, Periodontitis pathology, Periodontium immunology, Periodontium microbiology, Periodontium pathology, Plaque, Atherosclerotic immunology, Plaque, Atherosclerotic microbiology, Plaque, Atherosclerotic pathology, Porphyromonas gingivalis growth & development, Porphyromonas gingivalis immunology, Porphyromonas gingivalis pathogenicity, Treponema denticola growth & development, Treponema denticola immunology, Treponema denticola pathogenicity, Adventitia pathology, Antigens, Neoplasm immunology, Aorta pathology, Atherosclerosis complications, Integrins immunology, Periodontitis complications, Plaque, Atherosclerotic complications
- Abstract
The American Heart Association supports an association between periodontal diseases and atherosclerosis but not a causal association. This study explores the use of the integrin β6(-/-) mouse model to study the causality. We investigated the ability of a polymicrobial consortium of Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, and Fusobacterium nucleatum to colonize the periodontium and induce local and systemic inflammatory responses. Polymicrobially infected Itgβ6(-/-) mice demonstrate greater susceptibility to gingival colonization/infection, with severe gingival inflammation, apical migration of the junctional epithelium, periodontal pocket formation, alveolar bone resorption, osteoclast activation, bacterial invasion of the gingiva, a greater propensity for the bacteria to disseminate hematogenously, and a strong splenic T cell cytokine response. Levels of atherosclerosis risk factors, including serum nitric oxide, oxidized low-density lipoprotein, serum amyloid A, and lipid peroxidation, were significantly altered by polybacterial infection, demonstrating an enhanced potential for atherosclerotic plaque progression. Aortic gene expression revealed significant alterations in specific Toll-like receptor (TLR) and nucleotide-binding domain- and leucine-rich-repeat-containing receptor (NLR) pathway genes in response to periodontal bacterial infection. Histomorphometry of the aorta demonstrated larger atherosclerotic plaques in Itgβ6(-/-) mice than in wild-type (WT) mice but no significant difference in atherosclerotic plaque size between mice with polybacterial infection and mice with sham infection. Fluorescence in situ hybridization demonstrated active invasion of the aortic adventitial layer by P. gingivalis. Our observations suggest that polybacterial infection elicits distinct aortic TLR and inflammasome signaling and significantly increases local aortic oxidative stress. These results are the first to demonstrate the mechanism of the host aortic inflammatory response induced by polymicrobial infection with well-characterized periodontal pathogens., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)
- Published
- 2015
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150. Chlamydia pneumoniae Clinical Isolate from Gingival Crevicular Fluid: A Potential Atherogenic Strain.
- Author
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Filardo S, Di Pietro M, Schiavoni G, Minniti G, Ortolani E, Romano S, and Sessa R
- Subjects
- Animals, Cell Line, Chlamydophila pneumoniae classification, Chlamydophila pneumoniae genetics, Cytokines analysis, DNA, Bacterial chemistry, DNA, Bacterial genetics, Epithelial Cells microbiology, Genotype, Gingival Crevicular Fluid chemistry, Humans, Macrophages microbiology, Mice, Sequence Analysis, DNA, Atherosclerosis microbiology, Chlamydophila pneumoniae isolation & purification, Chlamydophila pneumoniae physiology, Chronic Periodontitis microbiology, Gingival Crevicular Fluid microbiology
- Abstract
Chlamydia pneumoniae has been associated to atherosclerotic cardiovascular diseases. The aim of our study was to characterize, for the first time, a C. pneumoniae strain isolated from the gingival crevicular fluid of a patient with chronic periodontitis, described as a risk factor for cardiovascular diseases. C. pneumoniae isolate was characterized and compared to the respiratory AR-39 strain by VD4-ompA genotyping and by investigating the intracellular growth in epithelial and macrophage cell lines and its ability to induce macrophage-derived foam cells. Inflammatory cytokine levels were determined in the gingival crevicular fluid sample. C. pneumoniae isolate showed a 99% similarity with the AR-39 strain in the VD4-ompA gene sequence and shared a comparable growth kinetic in epithelial cells and macrophages, as evidenced by the infectious progeny and by the number of chlamydial genomic copies. C. pneumoniae isolate significantly increased the number of foam cells as compared to uninfected and LDL-treated macrophages (45 vs. 6%, P = 0.0065) and to the AR-39 strain (45 vs. 30%, P = 0.0065). Significantly increased levels of interleukin 1-β (2.1 ± 0.3 pg/μL) and interleukin 6 (0.6 ± 0.08 pg/μL) were found. Our results suggest that C. pneumoniae may harbor inside oral cavity and potentially be atherogenic, even though further studies will be needed to clarify the involvement of C. pneumoniae in chronic periodontitis as a risk factor for cardiovascular diseases.
- Published
- 2015
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