2,554 results on '"renin–angiotensin–aldosterone system"'
Search Results
2. Walnut peptide relieves hypertension and associated kidney and heart injury by regulating the renin–angiotensin–aldosterone system and intestinal microbiota.
- Author
-
Chen, Shupeng, Huan, Pengtao, Ma, Ting, Zhong, Yujie, Ning, Delu, and Zhuang, Yongliang
- Abstract
BACKGROUND RESULTS CONCLUSION Hypertension is a chronic disease with high morbidity and mortality. Previously, we screened a walnut meal peptide FDWLR (PEP) with significant angiotensin‐converting enzyme inhibitory activity. The present study further investigated the anti‐hypertensive effects of PEP in vivo using spontaneously hypertensive rats.The results indicated that PEP reduced blood pressure and the indices in the renin–angiotensin–aldosterone system (RAAS) including angiotensin‐converting enzyme (ACE) (decreased by 15.36%), angiotensin II (Ang II) (decreased by 31.56%), angiotensinogen (AGT) (decreased by 58.84%) and aldosterone (ALD) (decreased by 18.27%), whereas NO levels increased by 54.96%. The pathological analysis showed that PEP relieved cardiac and renal damage. PEP also alleviated oxidative stress, inflammation and fibrosis in the heart and kidney. Mechanistically, PEP mitigated cardiac and renal damage by simultaneously regulating ACE‐Ang II‐AT1R and the ACE2‐Ang (1–7)‐MAS axis. Additionally, PEP increased the levels of short chain fatty acids by 224.16% and improved gut microbiota by increasing the abundance of Prevotella, Phascolarctobacterium, Clostridium_sensu_stricto and Bifidobacterium, at the same time as decreasing Bacteroides and Alistipes abundances.This study indicated that PEP prevented hypertension and associated heart and kidney damage by modulating the RAAS system and gut microbiota, which is valuable in guiding future development and optimal utilization of walnut meal. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
3. Untangling the Uncertain Role of Overactivation of the Renin–Angiotensin–Aldosterone System with the Aging Process Based on Sodium Wasting Human Models.
- Author
-
Thimm, Chantelle and Adjaye, James
- Abstract
Every individual at some point encounters the progressive biological process of aging, which is considered one of the major risk factors for common diseases. The main drivers of aging are oxidative stress, senescence, and reactive oxygen species (ROS). The renin–angiotensin–aldosterone system (RAAS) includes several systematic processes for the regulation of blood pressure, which is caused by an imbalance of electrolytes. During activation of the RAAS, binding of angiotensin II (ANG II) to angiotensin II type 1 receptor (AGTR1) activates intracellular nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to generate superoxide anions and promote uncoupling of endothelial nitric oxide (NO) synthase, which in turn decreases NO availability and increases ROS production. Promoting oxidative stress and DNA damage mediated by ANG II is tightly regulated. Individuals with sodium deficiency-associated diseases such as Gitelman syndrome (GS) and Bartter syndrome (BS) show downregulation of inflammation-related processes and have reduced oxidative stress and ROS. Additionally, the histone deacetylase sirtuin-1 (SIRT1) has a significant impact on the aging process, with reduced activity with age. However, GS/BS patients generally sustain higher levels of sirtuin-1 (SIRT1) activity than age-matched healthy individuals. SIRT1 expression in GS/BS patients tends to be higher than in healthy age-matched individuals; therefore, it can be assumed that there will be a trend towards healthy aging in these patients. In this review, we highlight the importance of the hallmarks of aging, inflammation, and the RAAS system in GS/BS patients and how this might impact healthy aging. We further propose future research directions for studying the etiology of GS/BS at the molecular level using patient-derived renal stem cells and induced pluripotent stem cells. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
4. Angiotensin II treatment of hypotension in noncardiac surgery: an initial dose-finding study.
- Author
-
Fernando, Rohesh J., Royster, Roger L., Ferrario, Carlos M., Saha, Amit K., Ahmad, Sarfaraz, Henshaw, Daryl S., Kittner, Sarah L., Talbott, Ashley L., Khanna, Ashish K., Morris, Benjamin N., Groban, Leanne, and Templeton, Thomas W.
- Subjects
- *
ANGIOTENSIN II , *HYPOTENSION , *SURGERY - Published
- 2024
- Full Text
- View/download PDF
5. Pathophysiological role of Na–Cl cotransporter in kidneys, blood pressure, and metabolism.
- Author
-
You, Ran and Jia, Zhanjun
- Subjects
KIDNEY physiology ,METABOLIC regulation ,BLOOD pressure ,ANTIHYPERTENSIVE agents ,HOMEOSTASIS - Abstract
The Na–Cl cotransporter (NCC) is a well-recognized regulator of ion transportation in the kidneys that facilitates Na
+ reabsorption in the distal convoluted tubule. It is also the pharmacologic inhibitory target of thiazide diuretics, a class of front-line antihypertensive agents that have been widely used for decades. NCC is a potent regulator of Na+ reabsorption and homeostasis. Hence, its overactivation and suppression lead to hypertension and hypotension, respectively. Genetic mutations that affect NCC function contribute to several diseases such as Gordon and Gitelman syndromes. We summarized the role of NCC in various physiologic processes and pathological conditions, such as maintaining ion and water homeostasis, controlling blood pressure, and influencing renal physiology and injury. In addition, we discussed the recent advancements in understanding cryo-EM structure of NCC, the regulatory mechanisms and binding mode of thiazides with NCC, and novel physiologic implications of NCC in regulating the cross-talk between the immune system and adipose tissue or the kidneys. This review contributes to a comprehensive understanding of the pivotal role of NCC in maintaining ion homeostasis, regulating blood pressure, and facilitating kidney function and NCC's novel role in immune and metabolic regulation. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
6. Mineralocorticoid receptor antagonists in kidney transplantation.
- Author
-
Kanbay, Mehmet, Copur, Sidar, Mizrak, Berk, Mallamaci, Francesca, and Zoccali, Carmine
- Subjects
- *
MINERALOCORTICOID receptors , *KIDNEY transplantation , *ANGIOTENSIN-receptor blockers , *ACE inhibitors , *CHRONIC kidney failure - Abstract
Background: The fundamental role of the renin–angiotensin–aldosterone system in the pathophysiology of chronic kidney disease, congestive heart failure, hypertension and proteinuria is well established in pre‐clinical and clinical studies. Mineralocorticoid receptor antagonists are among the primary options for renin–angiotensin–aldosterone system blockage, along with angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers. Methods: In this narrative review, we aim to evaluate the efficiency and safety of mineralocorticoid receptor antagonists in kidney transplant recipients, including the potential underlying pathophysiology. Results: The efficiency and safety of mineralocorticoid receptor antagonists in managing chronic kidney disease and proteinuria, either non‐nephrotic or nephrotic range, have been demonstrated among nontransplanted patients, though studies investigating the role of mineralocorticoid receptor antagonists among kidney transplant recipients are scarce. Nevertheless, promising results have been reported in pre‐clinical and clinical studies among kidney transplant recipients regarding the role of mineralocorticoid receptor antagonists in terms of ischaemia–reperfusion injury, proteinuria, or calcineurin inhibitor‐mediated nephrotoxicity without considerable adverse events such as hypotension, hyperkalaemia or worsening renal functions. Conclusion: Even though initial results regarding the role of mineralocorticoid receptor antagonist therapy for kidney transplant recipients are promising, there is clear need for large‐scale randomized clinical trials with long‐term follow‐up data. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
7. Nephrectomy and high-salt diet inducing pulmonary hypertension and kidney damage by increasing Ang II concentration in rats.
- Author
-
Jiang, Qian, Yang, Qifeng, Zhang, Chenting, Hou, Chi, Hong, Wei, Du, Min, Shan, Xiaoqian, Li, Xuanyi, Zhou, Dansha, Wen, Dongmei, Xiong, Yuanhui, Yang, Kai, Lin, Ziying, Song, Jingjing, Mo, Zhanjie, Feng, Huazhuo, Xing, Yue, Fu, Xin, Liu, Chunli, and Peng, Fang
- Abstract
Background: Chronic kidney disease (CKD) is a significant risk factor for pulmonary hypertension (PH), a complication that adversely affects patient prognosis. However, the mechanisms underlying this association remain poorly understood. A major obstacle to progress in this field is the lack of a reliable animal model replicating CKD-PH. Methods: This study aimed to establish a stable rat model of CKD-PH. We employed a combined approach, inducing CKD through a 5/6 nephrectomy and concurrently exposing the rats to a high-salt diet. The model's hemodynamics were evaluated dynamically, alongside a comprehensive assessment of pathological changes in multiple organs. Lung tissues and serum samples were collected from the CKD-PH rats to analyze the expression of angiotensin-converting enzyme 2 (ACE2), evaluate the activity of key vascular components within the renin–angiotensin–aldosterone system (RAAS), and characterize alterations in the serum metabolic profile. Results: At 14 weeks post-surgery, the CKD-PH rats displayed significant changes in hemodynamic parameters indicative of pulmonary arterial hypertension. Additionally, right ventricular hypertrophy was observed. Notably, no evidence of pulmonary vascular remodeling was found. Further analysis revealed RAAS dysregulation and downregulated ACE2 expression within the pulmonary vascular endothelium of CKD-PH rats. Moreover, the serum metabolic profile of these animals differed markedly from the sham surgery group. Conclusions: Our findings suggest that the development of pulmonary arterial hypertension in CKD-PH rats is likely a consequence of a combined effect: RAAS dysregulation, decreased ACE2 expression in pulmonary vascular endothelial cells, and metabolic disturbances. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
8. 单纯性肥胖儿童血清Leptin、25-(OH)D3与糖脂代谢、生长发育和肾素-血管紧张素-醛固酮系统的相关性分析.
- Author
-
王丽花, 苏艳花, 陈晓娟, 王 蕾, and 杨舒扬
- Subjects
- *
HIGH density lipoproteins , *LIPID metabolism , *CHILDHOOD obesity , *WAIST-hip ratio , *GLUCOSE metabolism - Abstract
Objective: To study the correlation between serum leptin (Leptin), 25-hydroxyvitamin D3 [25-(OH)D3] and glucose and lipid metabolism, growth and development and renin-angiotensin-aldosterone system (RAS) in children with simple obesity. Methods: 132 children with simple obesity admitted to Shanxi Children's Hospital from September 2021 to September 2023 were selected as observation group, and 100 healthy children who underwent physical examination during the same period were selected as control group. Serum Leptin, 25-(OH)D3, glucose and lipid metabolism indexes [fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C)] and RAS system indexes [renin (PRA), angiotensin-II (Ang-II), aldosterone (ALD)] were detected, and growth and development indexes [body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR)] were measured. The correlation between serum Leptin, 25-(OH)D3 and glucose and lipid metabolism, growth and development and RAS indexes in children with simple obesity were analyzed by Pearson test. Results: Serum Leptin in observation group was higher than that in control group, and 25-(OH)D3 was lower than that in control group (P<0.05). FBG, TG, TC and LDL-C in observation group were higher than those in control group, while HDL-C was lower than that in control group (P<0.05). BMI, WC and WHR in observation group were higher than those in control group(P<0.05). The PRA, Ang-II and ALD in observation group were higher than those in control group(P<0.05). Pearson test showed that, serum Leptin was positively correlated with FBG, TG, TC, LDL-C, BMI, WC, WHR, PRA, Ang-II and ALD, and negatively correlated with HDL-C, 25-(OH)D3 was negatively correlated with FBG, TG, TC, LDL-C, BMI, WC, WHR, PRA, Ang-II and ALD, and positively correlated with HDL-C(all P<0.05). Conclusion: In children with simple obesity, serum Leptin is highly express and 25-(OH)D3 is lowly express, which is closely relate to glucose and lipid metabolism, growth and development, and RAS system. Serum Leptin and 25-(OH)D3 may be involve in the pathogenesis of children with simple obesity by affecting glucose and lipid metabolism, growth and development and RAS system. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
9. Updates on the Renin–Angiotensin–Aldosterone System and the Cardiovascular Continuum.
- Author
-
Pop, Dana, Dădârlat-Pop, Alexandra, Tomoaia, Raluca, Zdrenghea, Dumitru, and Caloian, Bogdan
- Subjects
CARDIOVASCULAR diseases risk factors ,CORONARY disease ,MYOCARDIAL ischemia ,ANGIOTENSIN receptors ,CARDIOVASCULAR system - Abstract
The cardiovascular continuum describes how several cardiovascular risk factors contribute to the development of atherothrombosis, ischemic heart disease, and peripheral arteriopathy, leading to cardiac and renal failure and ultimately death. Due to its multiple valences, the renin–angiotensin–aldosterone system plays an important role in all stages of the cardiovascular continuum, starting from a cluster of cardiovascular risk factors, and continuing with the development of atherosclerosis thorough various mechanisms, and culminating with heart failure. Therefore, this article aims to analyze how certain components of the renin–angiotensin–aldosterone system (converting enzymes, angiotensin, angiotensin receptors, and aldosterone) are involved in the underlying pathophysiology of the cardiovascular continuum and the possible arrest of its progression. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
10. Nephrectomy and high-salt diet inducing pulmonary hypertension and kidney damage by increasing Ang II concentration in rats
- Author
-
Qian Jiang, Qifeng Yang, Chenting Zhang, Chi Hou, Wei Hong, Min Du, Xiaoqian Shan, Xuanyi Li, Dansha Zhou, Dongmei Wen, Yuanhui Xiong, Kai Yang, Ziying Lin, Jingjing Song, Zhanjie Mo, Huazhuo Feng, Yue Xing, Xin Fu, Chunli Liu, Fang Peng, Liling Wu, Bing Li, Wenju Lu, Jason X.-J. Yuan, Jian Wang, and Yuqin Chen
- Subjects
Chronic kidney disease ,Pulmonary hypertension ,Renin–angiotensin–aldosterone system ,Angiotensin converting enzyme 2 ,Metabolomics ,Diseases of the respiratory system ,RC705-779 - Abstract
Abstract Background Chronic kidney disease (CKD) is a significant risk factor for pulmonary hypertension (PH), a complication that adversely affects patient prognosis. However, the mechanisms underlying this association remain poorly understood. A major obstacle to progress in this field is the lack of a reliable animal model replicating CKD-PH. Methods This study aimed to establish a stable rat model of CKD-PH. We employed a combined approach, inducing CKD through a 5/6 nephrectomy and concurrently exposing the rats to a high-salt diet. The model's hemodynamics were evaluated dynamically, alongside a comprehensive assessment of pathological changes in multiple organs. Lung tissues and serum samples were collected from the CKD-PH rats to analyze the expression of angiotensin-converting enzyme 2 (ACE2), evaluate the activity of key vascular components within the renin–angiotensin–aldosterone system (RAAS), and characterize alterations in the serum metabolic profile. Results At 14 weeks post-surgery, the CKD-PH rats displayed significant changes in hemodynamic parameters indicative of pulmonary arterial hypertension. Additionally, right ventricular hypertrophy was observed. Notably, no evidence of pulmonary vascular remodeling was found. Further analysis revealed RAAS dysregulation and downregulated ACE2 expression within the pulmonary vascular endothelium of CKD-PH rats. Moreover, the serum metabolic profile of these animals differed markedly from the sham surgery group. Conclusions Our findings suggest that the development of pulmonary arterial hypertension in CKD-PH rats is likely a consequence of a combined effect: RAAS dysregulation, decreased ACE2 expression in pulmonary vascular endothelial cells, and metabolic disturbances. Graphical Abstract
- Published
- 2024
- Full Text
- View/download PDF
11. Cardiovascular Interactions of Renin-Angiotensin-Aldosterone System Assessed by Cardiac Magnetic Resonance: The Multi-Ethnic Study of Atherosclerosis.
- Author
-
Varadarajan, Vinithra, Marques, Mateus D, Venkatesh, Bharath Ambale, Allison, Matthew, Ostovaneh, Mohammad R, Yoneyama, Kihei, Donekal, Sirisha, Shah, Ravi V, Murthy, Venkatesh L, Wu, Colin O, Tracy, Russell P, Ouyang, Pamela, Rochitte, Carlos E, Bluemke, David A, and Lima, Joao AC
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Cardiovascular ,Atherosclerosis ,Aging ,Heart Disease ,Hypertension ,6.1 Pharmaceuticals ,Female ,Humans ,Middle Aged ,Aged ,Male ,Renin-Angiotensin System ,Renin ,Aldosterone ,Cardiovascular System ,Magnetic Resonance Spectroscopy ,blood pressure ,cardiac magnetic resonance imaging ,hypertension ,left atrium dysfunction ,left ventricle remodeling ,renin–angiotensin–aldosterone system ,vascular remodeling ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
BackgroundThe effects of the renin-angiotensin-aldosterone system in cardiovascular system have been described based on small studies. The aim of this study was to evaluate the relationship between aldosterone and plasma renin activity (PRA) and cardiovascular structure and function.MethodsWe studied a random sample of Multi-Ethnic Study of Atherosclerosis participants who had aldosterone and PRA blood assays at 2003-2005 and underwent cardiac magnetic resonance at 2010. Participants taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were excluded.ResultsThe aldosterone group was composed by 615 participants, mean age 61.6 ± 8.9 years, while the renin group was 580 participants, mean age 61.5 ± 8.8 years and both groups had roughly 50% females. In multivariable analysis, 1 SD increment of log-transformed aldosterone level was associated with 0.07 g/m2 higher left ventricle (LV) mass index (P = 0.04) and 0.11 ml/m2 higher left atrium (LA) minimal volume index (P < 0.01). Additionally, higher log-transformed aldosterone was associated with lower LA maximum strain and LA emptying fraction (P < 0.01). Aldosterone levels were not significantly associated with aortic measures. Log-transformed PRA was associated with lower LV end diastolic volume index (β standardized = 0.08, P = 0.05). PRA levels were not significantly associated with LA and aortic structural or functional differences.ConclusionsHigher levels of aldosterone and PRA are associated with concentric LV remodeling changes. Moreover, aldosterone was related to deleterious LA remodeling changes.
- Published
- 2023
12. Biological Pathways of Risk
- Author
-
Butts, Brittany, Dunbar, Sandra B., editor, and Braun, Lynne T., editor
- Published
- 2024
- Full Text
- View/download PDF
13. The angiotensin II receptors type 1 and 2 modulate astrocytes and their crosstalk with microglia and neurons in an in vitro model of ischemic stroke
- Author
-
Daniel Navin Olschewski, Nilufar Nazarzadeh, Felix Lange, Anna Maria Koenig, Christina Kulka, Jella-Andrea Abraham, Stefan Johannes Blaschke, Rudolf Merkel, Bernd Hoffmann, Gereon Rudolf Fink, Michael Schroeter, Maria Adele Rueger, and Sabine Ulrike Vay
- Subjects
Neuroinflammation ,Astrocytes ,Microglia ,Cortical neuronal network ,Cerebral ischemia ,Renin–angiotensin–aldosterone system ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Neurophysiology and neuropsychology ,QP351-495 - Abstract
Abstract Background Astrocytes are the most abundant cell type of the central nervous system and are fundamentally involved in homeostasis, neuroprotection, and synaptic plasticity. This regulatory function of astrocytes on their neighboring cells in the healthy brain is subject of current research. In the ischemic brain we assume disease specific differences in astrocytic acting. The renin–angiotensin–aldosterone system regulates arterial blood pressure through endothelial cells and perivascular musculature. Moreover, astrocytes express angiotensin II type 1 and 2 receptors. However, their role in astrocytic function has not yet been fully elucidated. We hypothesized that the angiotensin II receptors impact astrocyte function as revealed in an in vitro system mimicking cerebral ischemia. Astrocytes derived from neonatal wistar rats were exposed to telmisartan (angiotensin II type 1 receptor-blocker) or PD123319 (angiotensin II type 2 receptor-blocker) under normal conditions (control) or deprivation from oxygen and glucose. Conditioned medium (CM) of astrocytes was harvested to elucidate astrocyte-mediated indirect effects on microglia and cortical neurons. Result The blockade of angiotensin II type 1 receptor by telmisartan increased the survival of astrocytes during ischemic conditions in vitro without affecting their proliferation rate or disturbing their expression of S100A10, a marker of activation. The inhibition of the angiotensin II type 2 receptor pathway by PD123319 resulted in both increased expression of S100A10 and proliferation rate. The CM of telmisartan-treated astrocytes reduced the expression of pro-inflammatory mediators with simultaneous increase of anti-inflammatory markers in microglia. Increased neuronal activity was observed after treatment of neurons with CM of telmisartan- as well as PD123319-stimulated astrocytes. Conclusion Data show that angiotensin II receptors have functional relevance for astrocytes that differs in healthy and ischemic conditions and effects surrounding microglia and neuronal activity via secretory signals. Above that, this work emphasizes the strong interference of the different cells in the CNS and that targeting astrocytes might serve as a therapeutic strategy to influence the acting of glia-neuronal network in de- and regenerative context.
- Published
- 2024
- Full Text
- View/download PDF
14. Impaired angiotensin II signaling in septic shock
- Author
-
Adrien Picod, Bruno Garcia, Dirk Van Lier, Peter Pickkers, Antoine Herpain, Alexandre Mebazaa, and Feriel Azibani
- Subjects
Renin–angiotensin–aldosterone system ,Sepsis ,Septic shock ,Circulatory failure ,Angiotensin II ,Angiotensin-converting enzyme ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Abstract Recent years have seen a resurgence of interest for the renin–angiotensin–aldosterone system in critically ill patients. Emerging data suggest that this vital homeostatic system, which plays a crucial role in maintaining systemic and renal hemodynamics during stressful conditions, is altered in septic shock, ultimately leading to impaired angiotensin II—angiotensin II type 1 receptor signaling. Indeed, available evidence from both experimental models and human studies indicates that alterations in the renin–angiotensin–aldosterone system during septic shock can occur at three distinct levels: 1. Impaired generation of angiotensin II, possibly attributable to defects in angiotensin-converting enzyme activity; 2. Enhanced degradation of angiotensin II by peptidases; and/or 3. Unavailability of angiotensin II type 1 receptor due to internalization or reduced synthesis. These alterations can occur either independently or in combination, ultimately leading to an uncoupling between the renin–angiotensin–aldosterone system input and downstream angiotensin II type 1 receptor signaling. It remains unclear whether exogenous angiotensin II infusion can adequately address all these mechanisms, and additional interventions may be required. These observations open a new avenue of research and offer the potential for novel therapeutic strategies to improve patient prognosis. In the near future, a deeper understanding of renin–angiotensin–aldosterone system alterations in septic shock should help to decipher patients’ phenotypes and to implement targeted interventions.
- Published
- 2024
- Full Text
- View/download PDF
15. The angiotensin II receptors type 1 and 2 modulate astrocytes and their crosstalk with microglia and neurons in an in vitro model of ischemic stroke.
- Author
-
Olschewski, Daniel Navin, Nazarzadeh, Nilufar, Lange, Felix, Koenig, Anna Maria, Kulka, Christina, Abraham, Jella-Andrea, Blaschke, Stefan Johannes, Merkel, Rudolf, Hoffmann, Bernd, Fink, Gereon Rudolf, Schroeter, Michael, Rueger, Maria Adele, and Vay, Sabine Ulrike
- Subjects
- *
ASTROCYTES , *ANGIOTENSIN II , *ANGIOTENSIN receptors , *ISCHEMIC stroke , *MICROGLIA , *NEURONS - Abstract
Background: Astrocytes are the most abundant cell type of the central nervous system and are fundamentally involved in homeostasis, neuroprotection, and synaptic plasticity. This regulatory function of astrocytes on their neighboring cells in the healthy brain is subject of current research. In the ischemic brain we assume disease specific differences in astrocytic acting. The renin–angiotensin–aldosterone system regulates arterial blood pressure through endothelial cells and perivascular musculature. Moreover, astrocytes express angiotensin II type 1 and 2 receptors. However, their role in astrocytic function has not yet been fully elucidated. We hypothesized that the angiotensin II receptors impact astrocyte function as revealed in an in vitro system mimicking cerebral ischemia. Astrocytes derived from neonatal wistar rats were exposed to telmisartan (angiotensin II type 1 receptor-blocker) or PD123319 (angiotensin II type 2 receptor-blocker) under normal conditions (control) or deprivation from oxygen and glucose. Conditioned medium (CM) of astrocytes was harvested to elucidate astrocyte-mediated indirect effects on microglia and cortical neurons. Result: The blockade of angiotensin II type 1 receptor by telmisartan increased the survival of astrocytes during ischemic conditions in vitro without affecting their proliferation rate or disturbing their expression of S100A10, a marker of activation. The inhibition of the angiotensin II type 2 receptor pathway by PD123319 resulted in both increased expression of S100A10 and proliferation rate. The CM of telmisartan-treated astrocytes reduced the expression of pro-inflammatory mediators with simultaneous increase of anti-inflammatory markers in microglia. Increased neuronal activity was observed after treatment of neurons with CM of telmisartan- as well as PD123319-stimulated astrocytes. Conclusion: Data show that angiotensin II receptors have functional relevance for astrocytes that differs in healthy and ischemic conditions and effects surrounding microglia and neuronal activity via secretory signals. Above that, this work emphasizes the strong interference of the different cells in the CNS and that targeting astrocytes might serve as a therapeutic strategy to influence the acting of glia-neuronal network in de- and regenerative context. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
16. Impaired angiotensin II signaling in septic shock.
- Author
-
Picod, Adrien, Garcia, Bruno, Van Lier, Dirk, Pickkers, Peter, Herpain, Antoine, Mebazaa, Alexandre, and Azibani, Feriel
- Subjects
- *
RENIN-angiotensin system , *CRITICALLY ill , *PATIENTS , *HOMEOSTASIS , *ACE inhibitors , *CELLULAR signal transduction , *HEMODYNAMICS , *SEPTIC shock , *ANGIOTENSIN II , *ANGIOTENSIN converting enzyme , *PHENOTYPES , *DISEASE complications - Abstract
Recent years have seen a resurgence of interest for the renin–angiotensin–aldosterone system in critically ill patients. Emerging data suggest that this vital homeostatic system, which plays a crucial role in maintaining systemic and renal hemodynamics during stressful conditions, is altered in septic shock, ultimately leading to impaired angiotensin II—angiotensin II type 1 receptor signaling. Indeed, available evidence from both experimental models and human studies indicates that alterations in the renin–angiotensin–aldosterone system during septic shock can occur at three distinct levels: 1. Impaired generation of angiotensin II, possibly attributable to defects in angiotensin-converting enzyme activity; 2. Enhanced degradation of angiotensin II by peptidases; and/or 3. Unavailability of angiotensin II type 1 receptor due to internalization or reduced synthesis. These alterations can occur either independently or in combination, ultimately leading to an uncoupling between the renin–angiotensin–aldosterone system input and downstream angiotensin II type 1 receptor signaling. It remains unclear whether exogenous angiotensin II infusion can adequately address all these mechanisms, and additional interventions may be required. These observations open a new avenue of research and offer the potential for novel therapeutic strategies to improve patient prognosis. In the near future, a deeper understanding of renin–angiotensin–aldosterone system alterations in septic shock should help to decipher patients' phenotypes and to implement targeted interventions. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
17. Consensus statement on the management of hyperkalaemia—An Asia–Pacific perspective.
- Author
-
Yap, Desmond Y. H., Ma, Ronald C. W., Wong, Emmanuel C. K., Tsui, Matthew S. H., Yu, Esther Y. T., Yu, Vivien, Szeto, Cheuk Chun, Pang, Wing Fai, Tse, Hung Fat, Siu, David C. W., Tan, Kathryn C. B., Chen, Walter W. C., Li, Chiu Leong, Chen, Wei, and Chan, Tak Mao
- Subjects
- *
MEDICAL personnel , *CARDIAC arrest , *HYPERKALEMIA , *CHRONIC kidney failure , *RENIN-angiotensin system , *ARRHYTHMIA , *HEART failure - Abstract
Hyperkalaemia is an electrolyte imbalance that impairs muscle function and myocardial excitability, and can potentially lead to fatal arrhythmias and sudden cardiac death. The prevalence of hyperkalaemia is estimated to be 6%–7% worldwide and 7%–10% in Asia. Hyperkalaemia frequently affects patients with chronic kidney disease, heart failure, and diabetes mellitus, particularly those receiving treatment with renin‐angiotensin‐aldosterone system (RAAS) inhibitors. Both hyperkalaemia and interruption of RAAS inhibitor therapy are associated with increased risks for cardiovascular events, hospitalisations, and death, highlighting a clinical dilemma in high‐risk patients. Conventional potassium‐binding resins are widely used for the treatment of hyperkalaemia; however, caveats such as the unpalatable taste and the risk of gastrointestinal side effects limit their chronic use. Recent evidence suggests that, with a rapid onset of action and improved gastrointestinal tolerability, novel oral potassium binders (e.g., patiromer and sodium zirconium cyclosilicate) are alternative treatment options for both acute and chronic hyperkalaemia. To optimise the care for patients with hyperkalaemia in the Asia–Pacific region, a multidisciplinary expert panel was convened to review published literature, share clinical experiences, and ultimately formulate 25 consensus statements, covering three clinical areas: (i) risk factors of hyperkalaemia and risk stratification in susceptible patients; (ii) prevention of hyperkalaemia for at‐risk individuals; and (iii) correction of hyperkalaemia for at‐risk individuals with cardiorenal disease. These statements were expected to serve as useful guidance in the management of hyperkalaemia for health care providers in the region. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
18. Mechanisms of Kidney Damage Development in Patients with New Coronavirus Infection: Literature Review.
- Author
-
Utkina, E. V., Novakovskaya, V. V., Egorova, M. V., Fomina, N. V., and Chesnokova, L. D.
- Abstract
Every fourth person in the world currently has kidney problems to one or another degree. It is known that the novel coronavirus infection (COVID-19) is primarily a respiratory disease, but the kidney is a target organ. The coronavirus is tropic to kidney tissue due to the presence in the organ of RNA of angiotensin-converting enzyme type 2 and transmembrane serine protease 2, which is considered to be a target of this virus. The presence of renal failure in any stage is an independent unfavorable risk factor for contracting coronavirus and leads to a high frequency of hospitalization and mortality rate. Kidney failure is caused by various pathogenetic mechanisms: the direct cytopathic effect of the virus on their structures (podocytes, mesangial cells in the renal corpuscle, capillary endothelium in the glomerulus, epithelial cells in the proximal tubules), cytokine storm, damage to the renin–angiotensin–aldosterone system, and immunothrombosis. In many patients with confirmed coronavirus infection, from the first days of the disease, laboratory tests show significant changes in urine analysis (hematuria, proteinuria) and increased level of creatinine in the blood serum. The development of acute kidney injury is a main mortality risk factor. More research is needed into the exact effects of SARS-CoV-2 on the kidneys. Understanding the main pathogenetic pathways of their damage in COVID-19 is necessary to develop strategies and effective treatments. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
19. Unveiling Selected Influences on Chronic Kidney Disease Development and Progression.
- Author
-
Fularski, Piotr, Czarnik, Witold, Frankenstein, Hanna, Gąsior, Magdalena, Młynarska, Ewelina, Rysz, Jacek, and Franczyk, Beata
- Subjects
- *
CHRONIC kidney failure , *KIDNEY development , *ARTERIAL calcification , *DISEASE progression , *RENIN-angiotensin system , *DEEP brain stimulation - Abstract
Currently, more and more people are suffering from chronic kidney disease (CKD). It is estimated that CKD affects over 10% of the population worldwide. This is a significant issue, as the kidneys largely contribute to maintaining homeostasis by, among other things, regulating blood pressure, the pH of blood, and the water–electrolyte balance and by eliminating unnecessary metabolic waste products from blood. What is more, this disease does not show any specific symptoms at the beginning. The development of CKD is predisposed by certain conditions, such as diabetes mellitus or hypertension. However, these disorders are not the only factors promoting the onset and progression of CKD. The primary purpose of this review is to examine renin–angiotensin–aldosterone system (RAAS) activity, transforming growth factor-β1 (TGF-β1), vascular calcification (VC), uremic toxins, and hypertension in the context of their impact on the occurrence and the course of CKD. We firmly believe that a deeper comprehension of the cellular and molecular mechanisms underlying CKD can lead to an enhanced understanding of the disease. In the future, this may result in the development of medications targeting specific mechanisms involved in the decline of kidney function. Our paper unveils the selected processes responsible for the deterioration of renal filtration abilities. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
20. SIRT1在糖尿病心肌病发病中的研究进展.
- Author
-
解有成, 王菲, 徐进, and 于晓辉
- Abstract
Diabetic cardiomyopathy (DCM) is one of the most serious cardiovascular complications in diabetic patients, and it is also the main cause of increased mortality in diabetic patients, which has become a major global public health problem. As an important intracellular regulatory protein in body, sirtuin 1 (SIRT1) plays an important role in many biological processes, including reducing oxidative stress in cardiomyocytes, maintaining Ca2+ homeostasis in myocardial mitochondria, reducing myocardial endoplasmic reticulum stress, improving myocardial mitochondrial dysfunction, and inhibiting the activation of renin-angiotensin-aldosterone system. SIRT1 may be a potential therapeutic target for DCM. Further research targeting SIRT1 can provide a new theoretical basis for the clinical treatment of DCM. This article reviews the specific role of SIRT1 in the pathogenesis and treatment strategies of DCM. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
21. LOCAL ALDOSTERONE RELEASE AND CYP11B2 EXPRESSION IN RESPONSE TO ANGIOTENSIN PEPTIDES, GLUCOSE, AND POTASSIUM - AN EX VIVO STUDY ON MURINE COLON.
- Author
-
PANG, Z., KORPELA, R., and VAPAATALO, H.
- Abstract
We have previously described local aldosterone synthesis in mouse colon. In the renin-angiotensin-aldosterone system (RAAS), angiotensin II (Ang II) peptide is the physiological factor which stimulates aldosterone synthesis in the adrenal glands. We have recently demonstrated that Ang II stimulates aldosterone synthesis also in mouse colon. Here, we conducted a 75-min ex vivo incubation of murine colonic tissue and evaluated the effects of three other Ang peptides, Ang I (1 µM), Ang III (0.1 µM) and Ang (1-7) (0.1 µM) on aldosterone synthesis. As a possible mechanism, their effects on tissue levels of the rate-limiting enzyme, aldosterone synthase (CYP11B2) were measured by ELISA and Western blot. Ang III significantly elevated the amount of tissue CYP11B2 protein in colon. The values of released aldosterone in colon tissue incubation were increased over the control in the presence of Ang I, II or III, however, being statistically nonsignificant. In Western blot analysis, the values of tissue CYP11B2 protein content were elevated by Ang I and II. Ang (1-7) alone in colon did not influence CYP11B2 protein levels in the incubation experiment but showed higher aldosterone release without statistical significance. Ang (1-7) showed an antagonistic effect towards Ang II in release of aldosterone in adrenal gland. An overall estimation of a single peptide (three measured variables), the results were always in an increasing direction. The responses of aldosterone synthesis to high levels of glucose (44 mM) and potassium (18.8 mM) as physiological stimulators in vivo were investigated in the colon incubation. Glucose, equal to four times the concentration of the control buffer in the incubation, showed higher values of aldosterone release in colon than control without statistical significance similarly to the effect seen in adrenal glands. Increasing the concentration of potassium in the incubation buffer exerted no effect on colonic aldosterone production. Intriguingly, no correlation was found between aldosterone release and the tissue CYP11B2 protein content in colon. In summary, the response of colonic aldosterone synthesis to different Ang peptides resembles, but is not identical to, the situation in the adrenal glands. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
22. Blood Levels of Angiotensinogen and Hypertension in the Multi-Ethnic Study of Atherosclerosis (MESA)
- Author
-
Trainor, Patrick J, Brambatti, Michela, Carlisle, Samantha M, Mullick, Adam E, Shah, Sanjiv J, Kahlon, Tanvir, Mostacero, Diana Otero, Mousavi, Hossein, Morgan, Erin S, Tami, Yvonne, Michos, Erin D, Ouyang, Pamela, Tsimikas, Sotirios, and DeFilippis, Andrew P
- Subjects
Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Health Disparities ,Clinical Research ,Minority Health ,Women's Health ,Cardiovascular ,Atherosclerosis ,Hypertension ,Aging ,2.1 Biological and endogenous factors ,Male ,Adult ,Female ,Humans ,Angiotensinogen ,Aldosterone ,Renin-Angiotensin System ,Blood Pressure ,angiotensinogen ,blood pressure ,hypertensions ,renin-angiotensin-aldosterone system ,sex difference ,Cardiorespiratory Medicine and Haematology ,Public Health and Health Services ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology - Abstract
BackgroundAngiotensinogen is the proximal precursor of the angiotensin peptide hormones of the renin-angiotensin-aldosterone system (RAAS). Clinical trials are ongoing targeting angiotensinogen for the treatment of hypertension and heart failure. The epidemiology of angiotensinogen is not well defined, particularly its relationship to ethnicity, sex, and blood pressure (BP)/hypertension.ObjectivesThe authors sought to determine the relationship of circulating angiotensinogen levels to ethnicity, sex, BP, incident hypertension, and prevalent hypertension in a modern sex-balanced ethnically diverse cohort.MethodsPlasma angiotensinogen levels were measured in 5,786 participants from the MESA (Multi-Ethnic Study of Atherosclerosis). Linear, logistic, and Cox proportional hazards models were utilized to examine the associations of angiotensinogen with BP, prevalent hypertension, and incident hypertension, respectively.ResultsAngiotensinogen levels were significantly higher in females than males and differed across self-reported ethnicities with the ordering (from highest to lowest): White, Black, Hispanic, and Chinese adults. Higher levels were associated with higher BP and odds of prevalent hypertension, after adjusting for other risk factors. Equivalent relative differences in angiotensinogen were associated with greater differences in BP in males vs females. In males not taking RAAS-blocking medications, a standard deviation increment in log-angiotensinogen was associated with 2.61 mm Hg higher systolic BP (95% CI: 1.49-3.80), while in females the same increment in angiotensinogen was associated with 0.97 mm Hg higher systolic BP (95% CI: 0.30-1.65).ConclusionsSignificant differences in angiotensinogen levels are present between sexes and ethnicities. A positive association is present between levels and prevalent hypertension and BP, which differs between sexes.
- Published
- 2023
23. Dataset for discovering new hypertension small molecules using machine learning-aided computational fragment-based design
- Author
-
Odifentse Mapula-e Lehasa and Uche A.K. Chude-Okonkwo
- Subjects
Fragment-based drug discovery ,High blood pressure ,Renin-angiotensin-aldosterone system ,Angiotensin-converting enzyme inhibitor ,Angiotensin II receptor blockers ,K-Means clustering ,Computer applications to medicine. Medical informatics ,R858-859.7 ,Science (General) ,Q1-390 - Abstract
This dataset demonstrates the use of computational fragmentation-based and machine learning-aided drug discovery to generate new lead molecules for the treatment of hypertension. Specifically, the focus is on agents targeting the renin-angiotensin-aldosterone system (RAAS), commonly classified as Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Angiotensin II Receptor Blockers (ARBs). The preliminary dataset was a target-specific, user-generated fragment library of 63 molecular fragments of the 26 approved ACEI and ARB molecules obtained from the ChEMBL and DrugBank molecular databases. This fragment library provided the primary input dataset to generate the new lead molecules presented in the dataset. The newly generated molecules were screened to check whether they met the criteria for oral drugs and comprised the ACEI or ARB core functional group criterion. Using unsupervised machine learning, the molecules that met the criterion were divided into clusters of drug classes based on their functional group allocation. This process led to three final output datasets, one containing the new ACEI molecules, another for the new ARB molecules, and the last for the new unassigned class molecules. This data can aid in the timely and efficient design of novel antihypertensive drugs. It can also be used in precision hypertension medicine for patients with treatment resistance, non-response or co-morbidities. Although this dataset is specific to antihypertensive agents, the model can be reused with minimal changes to produce new lead molecules for other health conditions.
- Published
- 2024
- Full Text
- View/download PDF
24. The impact of GLP-1 receptor agonist liraglutide on blood pressure profile, hydration, natriuresis in diabetic patients with severely impaired kidney function
- Author
-
Małgorzata Wajdlich and Michał Nowicki
- Subjects
Liraglutide ,Diabetic kidney disease ,Blood pressure ,Natriuresis ,Renin–angiotensin–aldosterone system ,Medicine ,Science - Abstract
Abstract Chronic treatment with GLP-1R agonists may moderately lower blood pressure due to increased natriuresis and RAAS inhibition. Short-term effect of these drugs on blood pressure may be opposite and its mechanism remains unclear. We investigated the effect of a single dose of liraglutide on diurnal blood pressure profile, natriuresis, hydration and serum concentration of renin, aldosterone and atrial natriuretic peptide (ANP) in diabetic kidney disease (DKD). 17 patients with eGFR 60 ml/min/1.73 m2 received in a random order a single subcutaneous dose 1.2 mg liraglutide and placebo with subsequent 24 h blood pressure and natriuresis monitoring. Before and after each medication thoracic fluid index and plasma renin, aldosterone and ANP were also assessed. The blood pressure load in the daytime and nighttime were significantly increased after liraglutide compared to placebo in patients with eGFR 60 ml/min/1.73 m2 the changes of arterial pressure were comparable, while the morning surge was significantly reduced after liraglutide compared to placebo. After liraglutide 24 h urine sodium excretion increased in both groups vs. placebo (p 60 ml/min/1.73 m2. Plasma ANP increased after liraglutide in both groups, most in patients with eGFR
- Published
- 2024
- Full Text
- View/download PDF
25. Metabolic effects of aldosterone
- Author
-
K. V. Ivashchenko, N. V. Mazurina, N. M. Platonova, and E. A. Troshina
- Subjects
aldosterone ,obesity ,metabolic syndrome ,primary hyperaldosteronism ,glucose homeostasis ,fat tissue ,renin-angiotensin-aldosterone system ,Physiology ,QP1-981 ,Biochemistry ,QD415-436 - Abstract
Currently, increasing evidence shows the mutual influence of aldosterone and adipose tissue. Aldosterone excess has been reported in patients with obesity and metabolic syndrome. Aldosterone has a direct effect on adipose tissue increasing anabolic activity and expression of mineralocorticoid receptors. In turn, excessive activation of MCR leads to stimulation of adipogenesis and an increase in the volume of adipose tissue. Aldosterone excess can be considered an independent cardiovascular risk factor that affects such processes as cardiac fibrosis, nephrosclerosis, and arteriosclerosis. There is convincing evidence of higher prevalence and severity of impaired glucose homeostasis and lipid metabolism disorders among patients with primary hyperaldosteronism. Similar pathological changes are also observed in patients with obesity and metabolic syndrome. This review presents scientific data on the metabolic effects of aldosterone, in particular its effect on adipose tissue function, glucose and lipid metabolism. Treatment with mineralocorticoid receptor antagonists may provide substantial benefit in the management of metabolic syndrome, contribute to the stabilisation of glucose and lipid metabolism, improve clinical status of patients with cardiovascular diseases and reduce the risk of complications. However, available evidence from the conducted studies is not sufficient to justify introduction of such therapy into clinical practice.
- Published
- 2024
- Full Text
- View/download PDF
26. Prevalence of aldosterone breakthrough in dogs receiving renin‐angiotensin system inhibitors for proteinuric chronic kidney disease
- Author
-
Ames, Marisa K, Vaden, Shelly L, Atkins, Clarke E, Palerme, Jean‐Sebastien, Langston, Catherine E, Grauer, Gregory F, Shropshire, Sarah, Bove, Christina, and Webb, Tracy
- Subjects
Veterinary Sciences ,Agricultural ,Veterinary and Food Sciences ,Kidney Disease ,Hypertension ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Renal and urogenital ,Dogs ,Animals ,Aldosterone ,Renin-Angiotensin System ,Creatinine ,Prospective Studies ,Prevalence ,Antihypertensive Agents ,Proteinuria ,Renal Insufficiency ,Chronic ,Dog Diseases ,mineralocorticoid receptor antagonists ,nephrology ,renin-angiotensin-aldosterone system ,urine aldosterone to creatinine ratio ,Veterinary sciences - Abstract
BackgroundThe influence of aldosterone breakthrough (ABT) on proteinuria reduction during renin-angiotensin system (RAS) inhibition for spontaneous proteinuric chronic kidney disease (CKDP ) has not been determined in dogs.ObjectivesDetermine whether ABT occurs in dogs with CKDP and if it is associated with decreased efficacy in proteinuria reduction during RAS inhibitor treatment.AnimalsFifty-six client-owned dogs with CKDP and 31 healthy client-owned dogs.MethodsProspective, multicenter, open-label clinical trial. Dogs were treated with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker alone or in combination at the attending clinician's discretion and evaluated at 5 time points over 6 months. Healthy dogs were used to determine the urine aldosterone-to-creatinine ratio cutoff that defined ABT. The relationship of ABT (present at ≥50% of visits) and proteinuria outcome (≥50% reduction in urine protein-to-creatinine ratio from baseline at ≥50% of subsequent visits) was evaluated. Mixed effects logistic regression was used to evaluate the relationship between clinical variables and outcomes (either successful proteinuria reduction or ABT).ResultsThirty-six percent (20/56) of dogs had successful proteinuria reduction. Between 34% and 59% of dogs had ABT, depending on the definition used. Aldosterone breakthrough was not associated with proteinuria outcome. Longer duration in the study was associated with greater likelihood of successful proteinuria reduction (P = .002; odds ratio, 1.6; 95% confidence interval [CI], 1.2-2.2).Conclusions and clinical importanceAldosterone breakthrough was common in dogs receiving RAS inhibitors for CKDp but was not associated with proteinuria outcome.
- Published
- 2022
27. Genetic Factors Contributing to the Pathogenesis of Essential Hypertension in Two African Populations.
- Author
-
Kalideen, Kusha, Rayner, Brian, and Ramesar, Raj
- Subjects
- *
ESSENTIAL hypertension , *SOUTH Africans , *AFRICANS , *HYPERTENSION risk factors , *RENIN-angiotensin system , *GENETIC models - Abstract
The African continent has the highest prevalence of hypertension globally, with South Africa reporting the highest prevalence in Southern Africa. While the influence of genetic variability in the pathogenesis of hypertension is well described internationally, limited reports are available for African populations. This study aimed to assess the association of genetic variants and essential hypertension in a cohort of two ethnic South African population groups. Two hundred and seventy-seven hypertensive and one hundred and seventy-six normotensive individuals were genotyped for 78 variants. Genotyping was performed using the Illumina GoldenGate Assay and allele-specific polymerase chain reaction. The association of variants was assessed using the Fisher Exact test under the additive and allelic genetic models, while multivariate logistic regression was used to predict the development of hypertension. Five variants (CYP11B2 rs179998, AGT rs5051 and rs699, AGTR1 rs5186, and ACE rs4646994) were significantly associated with essential hypertension in the cohort under study. Furthermore, AGTR1 rs5186 and AGT rs699 were identified as risk factors for the development of hypertension in both ethnic groups. In two ethnic South African populations, an association was observed between renin–angiotensin–aldosterone system (RAAS)-related genes and the development of hypertension. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
28. Aldosterone and aldosterone synthase inhibitors in cardiorenal disease.
- Author
-
Verma, Subodh, Pandey, Avinash, Pandey, Arjun K., Butler, Javed, Lee, John S., Hwee Teoh, Mazer, C. David, Kosiborod, Mikhail N., Cosentino, Francesco, Anker, Stefan D., Connelly, Kim A., and Bhatt, Deepak L.
- Subjects
- *
ALDOSTERONE antagonists , *ALDOSTERONE , *CHRONIC kidney failure , *MINERALOCORTICOID receptors , *RENIN-angiotensin system , *HYPOTHALAMIC-pituitary-adrenal axis - Abstract
Modulation of the renin-angiotensin-aldosterone system is a foundation of therapy for cardiovascular and kidney diseases. Excess aldosterone plays an important role in cardiovascular disease, contributing to inflammation, fibrosis, and dysfunction in the heart, kidneys, and vasculature through both genomic and mineralocorticoid receptor (MR)-mediated as well as nongenomic mechanisms. MR antagonists have been a key therapy for attenuating the pathologic effects of aldosterone but are associated with some side effects and may not always adequately attenuate the nongenomic effects of aldosterone. Aldosterone is primarily synthesized by the CYP11B2 aldosterone synthase enzyme, which is very similar in structure to other enzymes involved in steroid biosynthesis including CYP11B1, a key enzyme involved in glucocorticoid production. Lack of specificity for CYP11B2, off-target effects on the hypothalamic-pituitary-adrenal axis, and counterproductive increased levels of bioactive steroid intermediates such as 11-deoxycorticosterone have posed challenges in the development of early aldosterone synthase inhibitors such as osilodrostat. In early-phase clinical trials, newer aldosterone synthase inhibitors demonstrated promise in lowering blood pressure in patients with treatment-resistant and uncontrolled hypertension. It is therefore plausible that these agents offer protection in other disease states including heart failure or chronic kidney disease. Further clinical evaluation will be needed to clarify the role of aldosterone synthase inhibitors, a promising class of agents that represent a potentially major therapeutic advance. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
29. Renoprotective Effects of Mineralocorticoid Receptor Antagonists Against Diabetic Kidney Disease.
- Author
-
Bayne, Sarah, LeFevre, James, Olstinske, Kayla, Ravindran, Sreenithya, and Munusamy, Shankar
- Subjects
DIABETIC nephropathies ,MINERALOCORTICOID receptors ,ANGIOTENSIN-receptor blockers ,GLUCAGON-like peptide 1 ,CHRONIC kidney failure ,TYPE 2 diabetes - Abstract
Diabetic kidney disease (DKD) is a growing epidemic worldwide and a leading cause of end‐stage kidney disease. Mineralocorticoid receptor (MR) blockade using Finerenone is a recently approved therapeutic approach to slow down the progression of DKD in patients with type 2 diabetes in addition to other therapies such as angiotensin‐II converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), sodium‐glucose co‐transporter 2 (SGLT2) inhibitors, and glucagon‐like peptide 1 (GLP‐1) analogs. This review elaborates on the pathophysiologic pathways activated by aldosterone (the human mineralocorticoid) in DKD, the pharmacology of three different generations of mineralocorticoid receptor antagonists (MRAs), specifically, spironolactone, eplerenone, and finerenone, and the mechanisms by which these MRAs elicit their protective effects on the kidney under diabetic settings. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
30. The sympathetic nervous system in heart failure revisited.
- Author
-
Triposkiadis, Filippos, Briasoulis, Alexandros, Kitai, Takeshi, Magouliotis, Dimitrios, Athanasiou, Thanos, Skoularigis, John, and Xanthopoulos, Andrew
- Subjects
SYMPATHETIC nervous system ,HEART failure ,SYSTEM failures ,RENIN-angiotensin system ,CARDIAC output ,VENTRICULAR ejection fraction - Abstract
Several attempts have been made, by the scientific community, to develop a unifying hypothesis that explains the clinical syndrome of heart failure (HF). The currently widely accepted neurohormonal model has substituted the cardiorenal and the cardiocirculatory models, which focused on salt-water retention and low cardiac output/peripheral vasoconstriction, respectively. According to the neurohormonal model, HF with eccentric left ventricular (LV) hypertrophy (LVH) (systolic HF or HF with reduced LV ejection fraction [LVEF] or HFrEF) develops and progresses because endogenous neurohormonal systems, predominantly the sympathetic nervous system (SNS) and the renin–angiotensin–aldosterone system (RAAS), exhibit prolonged activation following the initial heart injury exerting deleterious hemodynamic and direct nonhemodynamic cardiovascular effects. However, there is evidence to suggest that SNS overactivity often preexists HF development due to its association with HF risk factors, is also present in HF with preserved LVEF (diastolic HF or HFpEF), and that it is linked to immune/inflammatory factors. Furthermore, SNS activity in HF may be augmented by coexisting noncardiac morbidities and modified by genetic factors and demographics. The purpose of this paper is to provide a contemporary overview of the complex associations between SNS overactivity and the development and progression of HF, summarize the underlying mechanisms, and discuss the clinical implications as they relate to therapeutic interventions mitigating SNS overactivity. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
31. The GLP-1-mediated gut-kidney cross talk in humans: mechanistic insight.
- Author
-
Hinrichs, Gitte R., Hovind, Peter, and Asmar, Ali
- Subjects
- *
GLOMERULAR filtration rate , *PLASMA flow , *ANGIOTENSIN II , *INSULIN sensitivity , *KIDNEYS , *GLUCAGON-like peptide-1 agonists - Abstract
Incretin-based therapy is an antidiabetic and antiobesity approach mimicking glucagon-like peptide-1 (GLP-1) with additional endorgan protection. This review solely focuses on randomized, controlled mechanistic human studies, investigating the renal effects of GLP-1. There is no consensus about the localization of GLP-1 receptors (GLP-1Rs) in human kidneys. Rodent and primate data suggest GLP-1R distribution in smooth muscle cells in the preglomerular vasculature. Native GLP-1 and GLP-1R agonists elicit renal effects. Independently of renal plasma flow and glomerular filtration rate, GLP-1 has a natriuretic effect but only during volume expansion. This is associated with high renal extraction of GLP-1, suppression of angiotensin II, and increased medullary as well as cortical perfusion. These observations may potentially indicate that impaired GLP-1 sensing could establish a connection between salt sensitivity and insulin resistance. It is concluded that a functional GLP-1 kidney axis exists in humans, which may play a role in renoprotection. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
32. Histone Modifications and Their Contributions to Hypertension.
- Author
-
Ray, Atrayee, Stelloh, Cary, Yong Liu, Meyer, Alison, Geurts, Aron M., Cowley Jr., Allen W., Greene, Andrew S., Liang, Mingyu, and Rao, Sridhar
- Abstract
Essential hypertension, a multifaceted disorder, is a worldwide health problem. A complex network of genetic, epigenetic, physiological, and environmental components regulates blood pressure (BP), and any dysregulation of this network may result in hypertension. Growing evidence suggests a role for epigenetic factors in BP regulation. Any alterations in the expression or functions of these epigenetic regulators may dysregulate various determinants of BP, thereby promoting the development of hypertension. Histone posttranslational modifications are critical epigenetic regulators that have been implicated in hypertension. Several studies have demonstrated a clear association between the increased expression of some histone-modifying enzymes, especially HDACs (histone deacetylases), and hypertension. In addition, treatment with HDAC inhibitors lowers BP in hypertensive animal models, providing an excellent opportunity to design new drugs to treat hypertension. In this review, we discuss the potential contribution of different histone modifications to the regulation of BP. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
33. Methods Article for a Study Protocol: Study Design and Baseline Characteristics for Aldosterone Synthase Inhibition in Chronic Kidney Disease.
- Author
-
Tuttle, Katherine R., Rossing, Peter, Hauske, Sibylle J., Cronin, Lisa, Hussain, Joanna, de Zeeuw, Dick, and Heerspink, Hiddo J.L.
- Subjects
EMPAGLIFLOZIN ,CHRONIC kidney failure ,RESEARCH protocols ,ANGIOTENSIN-receptor blockers ,ACE inhibitors ,SODIUM-glucose cotransporter 2 inhibitors - Abstract
Introduction: Aldosterone synthase (AS) inhibition may overcome increased aldosterone production in response to renin-angiotensin system inhibition. BI 690517 is an AS inhibitor under investigation for chronic kidney disease (CKD). Methods: This multinational, phase II, double-blind study (NCT05182840) investigated the efficacy and safety of daily oral BI 690517, with or without empagliflozin 10 mg, in participants with CKD. The primary endpoint was change from baseline in urine albumin:creatinine ratio (UACR) at week 14. Between February 18, 2022, and December 30, 2022, 714 adults already treated by angiotensin-converting enzyme inhibitor (30.5%) or angiotensin receptor blocker (69.8%) were randomized (1:1) to an 8-week run-in to assign background empagliflozin (n = 356) or placebo (n = 358). Participants in each group were then randomized (1:1:1:1) to a 14-week treatment period with BI 690517 (3 mg, 10 mg, or 20 mg) or placebo. Of the 714 participants who entered run-in, 586 were randomized to the treatment period. They were predominantly men (66.6%) of white race (58.4%) with a mean (standard deviation [SD]) age of 63.8 (11.3) years. Type 2 diabetes was present in 414 participants (70.6%). The baseline mean (SD) estimated glomerular filtration rate was 51.9 (17.7) mL/min/1.73 m
2 , and median (interquartile range) UACR was 426.3 mg/g (205.3–888.5). Conclusion: This study will inform dose selection for further clinical development and determine whether BI 690517, with or without background empagliflozin, has a favorable safety profile and potential for additive kidney protection in participants with CKD already treated with a renin-angiotensin system inhibitor. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
34. Mechanisms and treatment of obesity-related hypertension—Part 1: Mechanisms.
- Author
-
Parvanova, Aneliya, Reseghetti, Elia, Abbate, Manuela, and Ruggenenti, Piero
- Subjects
- *
HYPERINSULINISM , *SYMPATHETIC nervous system , *OBESITY complications , *BAROREFLEXES , *DISEASE risk factors - Abstract
The prevalence of obesity has tripled over the past five decades. Obesity, especially visceral obesity, is closely related to hypertension, increasing the risk of primary (essential) hypertension by 65%–75%. Hypertension is a major risk factor for cardiovascular disease, the leading cause of death worldwide, and its prevalence is rapidly increasing following the pandemic rise in obesity. Although the causal relationship between obesity and high blood pressure (BP) is well established, the detailed mechanisms for such association are still under research. For more than 30 years sympathetic nervous system (SNS) and kidney sodium reabsorption activation, secondary to insulin resistance and compensatory hyperinsulinemia, have been considered as primary mediators of elevated BP in obesity. However, experimental and clinical data show that severe insulin resistance and hyperinsulinemia can occur in the absence of elevated BP, challenging the causal relationship between insulin resistance and hyperinsulinemia as the key factor linking obesity to hypertension. The purpose of Part 1 of this review is to summarize the available data on recently emerging mechanisms believed to contribute to obesity-related hypertension through increased sodium reabsorption and volume expansion, such as: physical compression of the kidney by perirenal/intrarenal fat and overactivation of the systemic/renal SNS and the renin–angiotensin–aldosterone system. The role of hyperleptinemia, impaired chemoreceptor and baroreceptor reflexes, and increased perivascular fat is also discussed. Specifically targeting these mechanisms may pave the way for a new therapeutic intervention in the treatment of obesity-related hypertension in the context of 'precision medicine' principles, which will be discussed in Part 2. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
35. RAAS in diabetic retinopathy: mechanisms and therapies
- Author
-
Xin Li, Yu-Hong Fu, Xue-Wei Tong, Yi-Tong Zhang, Yong-Yan Shan, Yu-Xin Xu, Sheng-Dan Pu, and Xin-Yuan Gao
- Subjects
Diabetic retinopathy ,renin-angiotensin-aldosterone system ,renin ,prorenin ,Medicine ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
ABSTRACT Diabetic retinopathy (DR) is a complication of diabetes with a complex pathophysiology and multiple factors involved. Recently, it has been found that the upregulation of the renin-angiotensin-aldosterone system (RAAS) leads to overexpression of angiotensin II (Ang II), which induces oxidative stress, inflammation, and angiogenesis in the retina. Therefore, RAAS may be a promising therapeutic target in DR. Notably, RAAS inhibitors are often used in the treatment of hypertension. Still, the potential role and mechanism of DR must be further studied. In this review, we discuss and summarize the pathology and potential therapeutic goals of RAAS in DR.
- Published
- 2024
- Full Text
- View/download PDF
36. A traditional Korean fermented food, Gochujang exerts anti-hypertensive effects, regardless of its high salt content by regulating renin-angiotensin-aldosterone system in SD rats
- Author
-
Jung Eun Park, Anna Han, Eun-Gyung Mun, and Youn-Soo Cha
- Subjects
Gochujang ,Hypertension ,Renin-angiotensin-aldosterone system ,Korean paradox ,Science (General) ,Q1-390 ,Social sciences (General) ,H1-99 - Abstract
The current study aimed to investigate the distinct outcomes of table salt and salt in Gochujang on blood pressure (BP). Animals were divided into 3 groups, including normal diet (NS, 0.5 % NaCl), high-salt diet (HS, normal diet with 8 % NaCl), or high-salt Gochujang diet (HSG, normal diet with Gochujang containing 8 % NaCl). Compared to the NS groups, the HS group showed significantly increased systolic blood pressure (SBP), while the HSG group did not elevate SBP. The HS group had lower serum angiotensin II and aldosterone levels than the NS group, while the HSG group showed higher levels of those parameters than the HS group. The renal mRNA expression related to the renin-angiotensin-aldosterone system (RAAS) was significantly higher in the HS group than the NS group, while the HSG group had markedly lower expression of those markers. The urinary and fecal Na+/K+ proportion was higher in both HS and HSG groups relative to the NS group, but the HSG group showed a decreased Na+/K+ ratio in urine and feces compared to the HS group. Moreover, the HS group had a significantly upregulated mRNA level of Na+/HCO3− co-transporter (Slc4a4) in the kidney than the NS group, whereas the HSG group showed downregulated mRNA expression of Slc4a4 compared to the HS group. This study demonstrates that Gochujang has anti-hypertensive effects regardless of its high salt content and provide the evidence regarding the distinct impacts between salt in Gochujang and the table salt.
- Published
- 2024
- Full Text
- View/download PDF
37. Reactive oxygen species impair Na+ transport and renal components of the renin-angiotensin-aldosterone system after paraquat poisoning
- Author
-
MARRY A.S. CIRILO, VALÉRIA B.S. SANTOS, NATÁLIA K.S. LIMA, HUMBERTO MUZI-FILHO, ANA D.O. PAIXÃO, ADALBERTO VIEYRA, and LEUCIO D. VIEIRA
- Subjects
Acute kidney injury ,reactive O2 species ,renal Na+-transporting ATPases ,renin-angiotensin-aldosterone system ,tempol ,Science - Abstract
Abstract Paraquat (1,1’-dimethyl-4,4’-bipyridyl dichloride) is an herbicide widely used worldwide and officially banned in Brazil in 2020. Kidney lesions frequently occur, leading to acute kidney injury (AKI) due to exacerbated reactive O2 species (ROS) production. However, the consequences of ROS exposure on ionic transport and the regulator local renin-angiotensin-aldosterone system (RAAS) still need to be elucidated at a molecular level. This study evaluated how ROS acutely influences Na+-transporting ATPases and the renal RAAS. Adult male Wistar rats received paraquat (20 mg/kg; ip). After 24 h, we observed body weight loss and elevation of urinary flow and serum creatinine. In the renal cortex, paraquat increased ROS levels, NADPH oxidase and (Na++K+)ATPase activities, angiotensin II-type 1 receptors, tumor necrosis factor-α (TNF-α), and interleukin-6. In the medulla, paraquat increased ROS levels and NADPH oxidase activity but inhibited (Na++K+)ATPase. Paraquat induced opposite effects on the ouabain-resistant Na+-ATPase in the cortex (decrease) and medulla (increase). These alterations, except for increased serum creatinine and renal levels of TNF-α and interleukin-6, were prevented by 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (tempol; 1 mmol/L in drinking water), a stable antioxidant. In summary, after paraquat poisoning, ROS production culminated with impaired medullary function, urinary fluid loss, and disruption of Na+-transporting ATPases and angiotensin II signaling.
- Published
- 2024
- Full Text
- View/download PDF
38. Significance of Haematological Variates in Determining Risk of Cardiovascular Complications Post SARS-CoV-2 Infection: A Prospective Cohort Study
- Author
-
Zia-ul-Sabah, Javed Iqbal, Shahid Aziz, Mohammad Muzaffar Mir, Humayoun Khan Durrani, Muad Ali Alfayea, Ayyub Ali Patel, and Tariq Rasool
- Subjects
acute cardiovascular syndrome ,acute respiratory distress syndrome ,catecholamine surge ,cytokine storm ,myocarditis ,renin-angiotensin-aldosterone system ,severe acute respiratory syndrome coronavirus-2 ,Medicine - Abstract
Introduction: Coronavirus Disease-2019 (COVID-19) is an ongoing global pandemic. Changes in haematological variables in patients with COVID-19 are emerging as important features of the disease. These changes in haematological variables may provide significant clues in the prognosis post Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. Aim: To determine the significance of various haematological variables in cardiac outcomes post SARS-CoV-2 infection. Materials and Methods: This was a prospective cohort study conducted at Prince Faisal bin Khalid Cardiac Centre, Abha, Kingdom of Saudi between March 2021 and October 2021. A total of 59 patients who were infected with SARS-CoV-2 with or without cardiac complaints were involved. Demographic, clinical, and laboratory data were recorded. Leukocyte counts, Neutrophil Counts, Lymphocyte counts, Neutrophil to Lymphocyte Ratio (NLR), platelet counts, Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), and D-Dimer were assessed and compared between subjects who developed Cardiovascular Complications (CVC+ group) and the subjects who did not develop CVC post SARS-CoV-2 infection (CVCgroup). Statistical analyses were performed using R scripting language and R Studio (version 1.2.5033, Orange Blossom). For continuous variables, t-test (for normally distributed) and MannWitney U test (for non normally distributed) were employed. For categorical data, Chi-square test (c2 ) was used. A p-value
- Published
- 2023
- Full Text
- View/download PDF
39. The role of mineralocorticoid receptors hyperactivation in the development of cardiorenal complications in patients with diabetes mellitus, perspective of the selective nonsteroidal mineralocorticoid receptors antagonist’s treatment: A review
- Author
-
Irina N. Bobkova
- Subjects
diabetes mellitus ,chronic kidney disease ,renin-angiotensin-aldosterone system ,mineralocorticoid receptors ,cardionephroprotection ,nonsteroidal mineralocorticoid receptors antagonists ,Medicine - Abstract
The renin-angiotensin-aldosterone system (RAAS) activation plays a key role in the chronic kidney disease (CKD) progression and in the cardiovascular complications (CVC) development in patients with diabetes mellitus (DM). RAAS blockers alone are not sufficient to prevent CVC and CVC progression. RAAS upregulation in CKD associated with DM triggers the mineralocorticoid receptors (MCR) hyperactivation which results in fibrosis and inflammation in the heart and kidneys. This review presents the current data about the variety of MCR hyperactivation manifestations, as well as about of multiplicity of MCR hyperactivation ways in DM. The efficacy and safety of finerenone, a new MCR nonsteroidal selective antagonist, are discussed.
- Published
- 2023
- Full Text
- View/download PDF
40. The renin-angiotensin-aldosterone system (RAAS) signaling pathways and cancer: foes versus allies
- Author
-
Bahareh Hassani, Zeinab Attar, and Negar Firouzabadi
- Subjects
Renin-angiotensin-aldosterone system ,Cancer biology ,ACE inhibitors ,ARBs, sex hormone-dependent cancer, GI cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Cytology ,QH573-671 - Abstract
Abstract The renin-angiotensin-aldosterone system (RAAS), is an old system with new fundamental roles in cancer biology which influences cell growth, migration, death, and metastasis. RAAS signaling enhances cell proliferation in malignancy directly and indirectly by affecting tumor cells and modulating angiogenesis. Cancer development may be influenced by the balance between the ACE/Ang II/AT1R and the ACE2/Ang 1–7/Mas receptor pathways. The interactions between Ang II/AT1R and Ang I/AT2R as well as Ang1-7/Mas and alamandine/MrgD receptors in the RAAS pathway can significantly impact the development of cancer. Ang I/AT2R, Ang1-7/Mas, and alamandine/MrgD interactions can have anticancer effects while Ang II/AT1R interactions can be involved in the development of cancer. Evidence suggests that inhibitors of the RAAS, which are conventionally used to treat cardiovascular diseases, may be beneficial in cancer therapies. Herein, we aim to provide a thorough description of the elements of RAAS and their molecular play in cancer. Alongside this, the role of RAAS components in sex-dependent cancers as well as GI cancers will be discussed with the hope of enlightening new venues for adjuvant cancer treatment. Graphical abstract
- Published
- 2023
- Full Text
- View/download PDF
41. Untangling the Uncertain Role of Overactivation of the Renin–Angiotensin–Aldosterone System with the Aging Process Based on Sodium Wasting Human Models
- Author
-
Chantelle Thimm and James Adjaye
- Subjects
sodium deficiency diseases ,distal convoluted tubules ,renin–angiotensin–aldosterone system ,ageing ,sodium accumulation ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Every individual at some point encounters the progressive biological process of aging, which is considered one of the major risk factors for common diseases. The main drivers of aging are oxidative stress, senescence, and reactive oxygen species (ROS). The renin–angiotensin–aldosterone system (RAAS) includes several systematic processes for the regulation of blood pressure, which is caused by an imbalance of electrolytes. During activation of the RAAS, binding of angiotensin II (ANG II) to angiotensin II type 1 receptor (AGTR1) activates intracellular nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to generate superoxide anions and promote uncoupling of endothelial nitric oxide (NO) synthase, which in turn decreases NO availability and increases ROS production. Promoting oxidative stress and DNA damage mediated by ANG II is tightly regulated. Individuals with sodium deficiency-associated diseases such as Gitelman syndrome (GS) and Bartter syndrome (BS) show downregulation of inflammation-related processes and have reduced oxidative stress and ROS. Additionally, the histone deacetylase sirtuin-1 (SIRT1) has a significant impact on the aging process, with reduced activity with age. However, GS/BS patients generally sustain higher levels of sirtuin-1 (SIRT1) activity than age-matched healthy individuals. SIRT1 expression in GS/BS patients tends to be higher than in healthy age-matched individuals; therefore, it can be assumed that there will be a trend towards healthy aging in these patients. In this review, we highlight the importance of the hallmarks of aging, inflammation, and the RAAS system in GS/BS patients and how this might impact healthy aging. We further propose future research directions for studying the etiology of GS/BS at the molecular level using patient-derived renal stem cells and induced pluripotent stem cells.
- Published
- 2024
- Full Text
- View/download PDF
42. Combining Bibliometric Analysis to Uncover the Detrimental and Protective Roles of Various Dendritic Cell Types in Cardiovascular Arterial Diseases
- Author
-
Wenxing Li, Lan Luo, Yue Fan, Xiangling Lv, Qianfeng Jiang, and Yang Jiao
- Subjects
dendritic cells ,chemokines ,renin-angiotensin-aldosterone system ,hypertension ,acute coronary syndrome ,Biochemistry ,QD415-436 ,Biology (General) ,QH301-705.5 - Abstract
Immune cell dysregulation is increasingly recognized as a pivotal pathological factor in cardiovascular disease. Over the past decade, a surge of research has focused on the role of immune cells such as dendritic cells (DCs), T cells, macrophages, and neutrophils in cardiovascular diseases, findings that are frequently featured in leading cardiology journals. This review provides a comprehensive synthesis of the roles that DCs play in common and potentially fatal arterial diseases, including hypertension, coronary artery atherosclerosis, acute coronary syndrome, pulmonary arterial hypertension, aortic aneurysm, aortic dissection, and vasculitis. Combining with bibliometric analysis, this review delves into the critical mechanisms by which DCs contribute to these diseases and reveals the shared mechanisms across diverse diseases. This review also offers new advances in clinical treatment strategies involving DCs.
- Published
- 2024
- Full Text
- View/download PDF
43. Updates on the Renin–Angiotensin–Aldosterone System and the Cardiovascular Continuum
- Author
-
Dana Pop, Alexandra Dădârlat-Pop, Raluca Tomoaia, Dumitru Zdrenghea, and Bogdan Caloian
- Subjects
renin–angiotensin–aldosterone system ,cardiovascular risk factors ,stroke ,heart failure ,atrial fibrillation ,Biology (General) ,QH301-705.5 - Abstract
The cardiovascular continuum describes how several cardiovascular risk factors contribute to the development of atherothrombosis, ischemic heart disease, and peripheral arteriopathy, leading to cardiac and renal failure and ultimately death. Due to its multiple valences, the renin–angiotensin–aldosterone system plays an important role in all stages of the cardiovascular continuum, starting from a cluster of cardiovascular risk factors, and continuing with the development of atherosclerosis thorough various mechanisms, and culminating with heart failure. Therefore, this article aims to analyze how certain components of the renin–angiotensin–aldosterone system (converting enzymes, angiotensin, angiotensin receptors, and aldosterone) are involved in the underlying pathophysiology of the cardiovascular continuum and the possible arrest of its progression.
- Published
- 2024
- Full Text
- View/download PDF
44. Renin-Angiotensin-Aldosterone System Activation and Diuretic Response in Ambulatory Patients With Heart Failure
- Author
-
Amatruda, Jonathan G, Scherzer, Rebecca, Rao, Veena S, Ivey-Miranda, Juan B, Shlipak, Michael G, Estrella, Michelle M, and Testani, Jeffrey M
- Subjects
Cardiovascular ,Hypertension ,Heart Disease ,Clinical Research ,Cardiorenal syndrome ,diuretic resistance ,heart failure ,loop diuretics ,natriuresis ,renin-angiotensin-aldosterone system ,torsemide - Abstract
Rationale & objectiveHeart failure treatment relies on loop diuretics to induce natriuresis and decongestion, but the therapy is often limited by diuretic resistance. We explored the association of renin-angiotensin-aldosterone system (RAAS) activation with diuretic response.Study designObservational cohort.Setting & populationEuvolemic ambulatory adults with chronic heart failure were administered torsemide in a monitored environment.PredictorsPlasma total renin, active renin, angiotensinogen, and aldosterone levels. Urine total renin and angiotensinogen levels.OutcomesSodium output per doubling of diuretic dose and fractional excretion of sodium per doubling of diuretic dose.Analytical approachRobust linear regression models estimated the associations of each RAAS intermediate with outcomes.ResultsThe analysis included 56 participants, and the median age was 65 years; 50% were women, and 41% were Black. The median home diuretic dose was 80-mg furosemide equivalents. In unadjusted and multivariable-adjusted models, higher levels of RAAS measures were generally associated with lower diuretic efficiency. Higher plasma total renin remained significantly associated with lower sodium output per doubling of diuretic dose (β = -0.41 [-0.76, -0.059] per SD change) with adjustment; higher plasma total and active renin were significantly associated with lower fractional excretion of sodium per doubling of diuretic dose (β = -0.48 [-0.83, -0.14] and β = -0.51 [-0.95, -0.08], respectively) in adjusted models. Stratification by RAAS inhibitor use did not substantially alter these associations.LimitationsSmall sample size; highly selected participants; associations may not be causal.ConclusionsAmong multiple measures of RAAS activation, higher plasma total and active renin levels were consistently associated with lower diuretic response. These findings highlight the potential drivers of diuretic resistance and underscore the need for high-quality trials of decongestive therapy enhanced by RAAS blockade.
- Published
- 2022
45. Newer COVID-19 vaccines: Still lights and shadows?
- Author
-
Angeli, Fabio, Zappa, Martina, and Verdecchia, Paolo
- Subjects
- *
COVID-19 vaccines , *RENIN-angiotensin system , *BLOOD pressure , *ANGIOTENSIN converting enzyme - Published
- 2023
- Full Text
- View/download PDF
46. Soyasaponin I alleviates hypertensive intracerebral hemorrhage by inhibiting the renin-angiotensin-aldosterone system.
- Author
-
Wei Li, Shao-Guang Li, Lan Li, Li-Jian Yang, Zeng-Shi Li, Xi Li, An-Yuan Ye, Yang Xiong, Yi Zhang, and Yuan-Yuan Xiong
- Subjects
- *
CEREBRAL hemorrhage , *RENIN-angiotensin system , *HEMATOXYLIN & eosin staining , *ENZYME-linked immunosorbent assay , *HYPERTENSION , *ANGIOTENSIN-receptor blockers - Abstract
Background: Hypertensive intracerebral hemorrhage (HICH) is a life-threatening disease and lacks effective treatments. Previous studies have confirmed that metabolic profiles altered after ischemic stroke, but how brain metabolism changes after HICH was unclear. This study aimed to explore the metabolic profiles after HICH and the therapeutic effects of soyasaponin I on HICH. Methods: HICH model was established first. Hematoxylin and eosin staining was used to estimate the pathological changes after HICH. Western blot and Evans blue extravasation assay were applied to determine the integrity of the blood-brain barrier (BBB). Enzyme-linked immunosorbent assay was used to detect the activation of the renin-angiotensin-aldosterone system (RAAS). Next, liquid chromatography-mass spectrometry-untargeted metabolomics was utilized to analyze the metabolic profiles of brain tissues after HICH. Finally, soyasaponin I was administered to HICH rats, and the severity of HICH and activation of the RAAS were further assessed. Results: We successfully constructed HICH model. HICH significantly impaired BBB integrity and activated RAAS. HICH increased PE(14:0/24:1(15Z)), arachidonoyl serinol, PS(18:0/22:6(4Z, 7Z, 10Z, 13Z, 16Z, and 19Z)), PS(20:1(11Z)/20:5(5Z, 8Z, 11Z, 14Z, and 17Z)), glucose 1-phosphate, etc., in the brain, whereas decreased creatine, tripamide, D-N-(carboxyacetyl)alanine, N-acetylaspartate, N-acetylaspartylglutamic acid, and so on in the hemorrhagic hemisphere. Cerebral soyasaponin I was found to be downregulated after HICH and supplementation of soyasaponin I inactivated the RAAS and alleviated HICH. Conclusion: The metabolic profiles of the brains changed after HICH. Soyasaponin I alleviated HICH via inhibiting the RAAS and may serve as an effective drug for the treatment of HICH in the future. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
47. Parasympathetic activity and total fibrotic kidney in autosomal-dominant polycystic kidney disease patients: a pilot study.
- Author
-
Lai, Silvia, Perrotta, Adolfo Marco, Panebianco, Valeria, Mazzaferro, Sandro, Menè, Paolo, Pellicano, Chiara, Tinti, Francesca, Muscaritoli, Maurizio, Cianci, Rosario, and Gigante, Antonietta
- Abstract
Purpose: Renin–angiotensin system hyperactivation in autosomal-dominant polycystic kidney disease (ADPKD) patients leads to early hypertension. Cystic enlargement probably causes parenchymal hypoxia, renin secretion, and endothelial dysfunction. Sympathetic and parasympathetic balance is altered in this condition, especially during the night, also affecting blood pressure circadian rhythm. Aim of this study was to evaluate sympathetic/parasympathetic balance using heart rate variability (HRV) parameters and find a correlation between HRV and renal damage progression, as total kidney volume enlargement, in ADPKD patients. Methods: Sixteen adult ADPKD patients were enrolled in the study. Eleven patients (68.8%) were male, and the median age was 42 years (IQR 36–47.5). HRV parameters were calculated using 24 h-ECG Holter. A kidney magnetic resonance imaging (MRI) scan 3 Tesla was performed to evaluate total kidney volume (TKV) and total fibrotic volume (TFV). Results: A statistically significant positive linear correlation was observed between length of kidneys and frequency domain parameters as low frequency (LF) (r = 0.595, p < 0.05) and LFday (r = 0.587, p < 0.05). Moreover, a statistically significant positive linear correlation exists between high frequency (HF) and TFV (r = 0.804, p < 0.01) or height-adjusted (ha) TFV (r = 0.801, p < 0.01). Finally, we found a statistically significant positive linear correlation between HFnight and TKV (r = 0.608, p < 0.05), ha-TKV (r = 0.685, p < 0.01), TFV (r = 0.594, p < 0.05), and ha-TFV (r = 0.615, p < 0.05). Conclusion: We suppose that the increase in TKV and TFV could lead to a parasympathetic tone hyperactivation, probably in response to hypoxic stress and vasoconstriction due to cystic enlargement. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
48. The renin-angiotensin-aldosterone system (RAAS) signaling pathways and cancer: foes versus allies.
- Author
-
Hassani, Bahareh, Attar, Zeinab, and Firouzabadi, Negar
- Subjects
- *
RENIN-angiotensin system , *CELLULAR signal transduction , *ADJUVANT treatment of cancer , *CARCINOGENESIS , *CELL growth , *CARDIOVASCULAR diseases - Abstract
The renin-angiotensin-aldosterone system (RAAS), is an old system with new fundamental roles in cancer biology which influences cell growth, migration, death, and metastasis. RAAS signaling enhances cell proliferation in malignancy directly and indirectly by affecting tumor cells and modulating angiogenesis. Cancer development may be influenced by the balance between the ACE/Ang II/AT1R and the ACE2/Ang 1–7/Mas receptor pathways. The interactions between Ang II/AT1R and Ang I/AT2R as well as Ang1-7/Mas and alamandine/MrgD receptors in the RAAS pathway can significantly impact the development of cancer. Ang I/AT2R, Ang1-7/Mas, and alamandine/MrgD interactions can have anticancer effects while Ang II/AT1R interactions can be involved in the development of cancer. Evidence suggests that inhibitors of the RAAS, which are conventionally used to treat cardiovascular diseases, may be beneficial in cancer therapies. Herein, we aim to provide a thorough description of the elements of RAAS and their molecular play in cancer. Alongside this, the role of RAAS components in sex-dependent cancers as well as GI cancers will be discussed with the hope of enlightening new venues for adjuvant cancer treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
49. Randomized Placebo-Controlled Trial to Evaluate Effects of Eplerenone on Myocardial Perfusion and Function Among Persons With Human Immunodeficiency Virus (HIV)—Results From the MIRACLE HIV Study.
- Author
-
Srinivasa, Suman, Walpert, Allie R, Thomas, Teressa S, Huck, Daniel M, Jerosch-Herold, Michael, Islam, Sabeeh, Lu, Michael T, Burdo, Tricia H, deFilippi, Christopher R, Dunderdale, Carolyn N, Feldpausch, Meghan, Iyengar, Sanjna, Shen, Grace, Baak, Stephen, Torriani, Martin, Robbins, Gregory K, Lee, Hang, Kwong, Raymond, DiCarli, Marcelo, and Adler, Gail K
- Subjects
- *
MYOCARDIUM physiology , *HIV infections , *DIURETICS , *HIV-positive persons , *TROPONIN , *CARDIOVASCULAR diseases , *MYOCARDIAL injury , *ANTIRETROVIRAL agents , *MAGNETIC resonance imaging , *RENIN-angiotensin system , *CORONARY circulation , *TREATMENT effectiveness , *RANDOMIZED controlled trials , *PLACEBOS , *RESEARCH funding , *POSITRON emission tomography , *DESCRIPTIVE statistics , *HEART function tests , *STATISTICAL sampling , *PERFUSION imaging , *T cells , *PERFUSION , *EVALUATION - Abstract
Background Increased renin angiotensin aldosterone system (RAAS) activity may contribute to excess cardiovascular disease in people with HIV (PWH). We investigated how RAAS blockade may improve myocardial perfusion, injury, and function among well-treated PWH. Methods Forty PWH, on stable ART, without known heart disease were randomized to eplerenone 50 mg PO BID (n = 20) or identical placebo (n = 20) for 12 months. The primary endpoints were (1) myocardial perfusion assessed by coronary flow reserve (CFR) on cardiac PET or stress myocardial blood flow (sMBF) on cardiac MRI or (2) myocardial inflammation by extracellular mass index (ECM i) on cardiac MRI. Results Beneficial effects on myocardial perfusion were seen for sMBF by cardiac MRI (mean [SD]: 0.09 [0.56] vs −0.53 [0.68] mL/min/g; P =.03) but not CFR by cardiac PET (0.01 [0.64] vs −0.07 [0.48]; P =.72, eplerenone vs placebo). Eplerenone improved parameters of myocardial function on cardiac MRI including left ventricular end diastolic volume (−13 [28] vs 10 [26] mL; P =.03) and global circumferential strain (GCS; median [interquartile range 25th–75th]: −1.3% [−2.9%–1.0%] vs 2.3% [−0.4%–4.1%]; P =.03), eplerenone versus placebo respectively. On cardiac MRI, improvement in sMBF related to improvement in global circumferential strain (ρ = −0.65, P =.057) among those treated with eplerenone. Selecting for those with impaired myocardial perfusion (CFR <2.5 and/or sMBF <1.8), there was a treatment effect of eplerenone versus placebo to improve CFR (0.28 [0.27] vs −0.05 [0.36]; P =.04). Eplerenone prevented a small increase in troponin (0.00 [−0.13–0.00] vs 0.00 [0.00–0.74] ng/L; P =.03) without effects on ECM i (0.9 [−2.3–4.3] vs −0.7 [−2.2–−0.1] g/m2; P =.38). CD4+ T-cell count (127 [−38–286] vs −6 [−168–53] cells/μL; P =.02) increased in the eplerenone- versus placebo-treated groups. Conclusions RAAS blockade with eplerenone benefitted key indices and prevented worsening of myocardial perfusion, injury, and function among PWH with subclinical cardiac disease when compared with placebo. Clinical Trials Registration NCT02740179 (https://clinicaltrials.gov/ct2/show/NCT02740179?term=NCT02740179&draw=2&rank=1). [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
50. ACE2 PET in healthy and diseased conditions.
- Author
-
Li, Rou, Xu, Aijing, Cheng, Chao, Chen, Jian, Wang, Mingxin, Luo, Xiu, Liang, Siyu, Hou, Wenli, Cui, Bin, Feng, Yu, Zuo, Changjing, and Li, Xiao
- Abstract
Angiotensin converting enzyme 2 (ACE2) played a critical role in regulating renin‐angiotensin‐aldosterone system (RAAS). In this research, 68Ga‐cyc‐DX600 was synthesized as PET tracer of ACE2 imaging. ACE2 positron emission tomography/magnetic resonance (PET/MR) was preliminary administered on twelve healthy volunteers, and the images were normalized and registered to establish the standard model of ACE2 PET. In diseased conditions, 68Ga‐cyc‐DX600 PET and 18F‐FDG PET were compared for COVID‐19 (one in acute phase and three in post‐COVID), anemia (n = 1) and malignancies (n = 2) to evaluate the diagnostic efficiency. 68Ga‐cyc‐DX600 PET was of a definite ACE2 dependence. For the tracer uptake of ACE2 PET/MR of female and male, differences existed in salivary glands, upper respiratory tract and kidneys, meanwhile, age, and body mass index (BMI) were also the confounding factors. RAAS‐related tissue and organs were of the relatively higher tracer uptake, such as SUVmean of cardiac chamber (3.786 ± 1.495), liver (5.342 ± 2.267), spleen (4.465 ± 2.508), and kidney (4.906 ± 1.619 for female and 8.431 ± 5.179 for male). For COVID‐19, ACE2 PET revealed ACE2 fluctuations, particularly in the susceptible organs, including liver, spleen and testis. In the case of anemia, the activated local RAS in the bone marrow was of diffuse high tracer uptake. ACE2 PET of malignancies added supplementary information to FDG PET. 68Ga‐cyc‐DX600‐based ACE2 PET models were established for visually monitoring of whole‐body ACE2 expression. The feasibility of ACE2 PET in supervising disease was primarily proved in COVID‐19, anemia and malignancies as providing a comprehensive view on the disease process and functional recovery. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.