445 results on '"M. Björck"'
Search Results
2. Predictive machine learning models for ascending aortic dilatation in patients with bicuspid and tricuspid aortic valves undergoing cardiothoracic surgery: a prospective, single-centre and observational study
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Anders Franco-Cereceda, Kenneth Caidahl, Bamba Gaye, Per Eriksson, Magalie Ladouceur, Christian Olsson, Hanna M Björck, Maxime Vignac, and Jesper R Gådin
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Medicine - Abstract
Objectives The objective of this study was to develop clinical classifiers aiming to identify prevalent ascending aortic dilatation in patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV).Design and setting A prospective, single-centre and observational cohort.Participants The study involved 543 BAV and 491 TAV patients with aortic valve disease and/or ascending aortic dilatation, excluding those with coronary artery disease, undergoing cardiothoracic surgery at the Karolinska University Hospital (Sweden).Main outcome measures Predictors of high risk of ascending aortic dilatation (defined as ascending aorta with a diameter above 40 mm) were identified through the application of machine learning algorithms and classic logistic regression models.Exposures Comprehensive multidimensional data, including valve morphology, clinical information, family history of cardiovascular diseases, prevalent diseases, demographic details, lifestyle factors, and medication.Results BAV patients, with an average age of 60.4±12.4 years, showed a higher frequency of aortic dilatation (45.3%) compared with TAV patients, who had an average age of 70.4±9.1 years (28.9% dilatation, p
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- 2024
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3. Acetylsalicylic Acid Is Associated With a Lower Prevalence of Ascending Aortic Aneurysm and a Decreased Aortic Expression of Cyclooxygenase 2
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Carl Granath, David Freiholtz, Fredrik Bredin, Christian Olsson, Anders Franco‐Cereceda, and Hanna M. Björck
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ascending aortic aneurysm ,aspirin ,COX‐2 ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Acetylsalicylic acid (ASA) therapy has been associated with a reduced prevalence and growth rate of abdominal as well as intracranial aneurysms, but the relationship between ASA and ascending aortic aneurysm formation remains largely unknown. The aim of the present study was to investigate whether ASA therapy is associated with a lower prevalence of ascending aortic aneurysm in a surgical cohort. Methods and Results One thousand seven hundred patients undergoing open‐heart surgery for ascending aortic aneurysm and/or aortic valve disease were studied in this retrospective cross‐sectional study. Aortic dilatation was defined as an aortic root or ascending aortic diameter ≥45 mm. Medications were self‐reported by the patients in a systematic questionnaire. Cyclooxygenase gene expression was measured in the intima‐media portion of the ascending aorta (n=117). In a multivariable analysis, ASA was associated with a reduced prevalence of ascending aortic aneurysm (relative risk, 0.68 [95% CI, 0.48–0.95], P=0.026) in patients with tricuspid aortic valves, but not in patients with bicuspid aortic valves (relative risk, 0.93 [95% CI, 0.64–1.34], P=0.687). Intima‐media cyclooxygenase expression was positively correlated with ascending aortic dimensions (P
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- 2022
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4. Valve disease and aortopathy associations of bicuspid aortic valve phenotypes differ between men and women
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Anders Franco-Cereceda, Luc Mertens, Christian Olsson, Carl Granath, Salah A Mohamed, Michael Grattan, and Hanna M Björck
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2021
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5. Endothelial/Epithelial Mesenchymal Transition in Ascending Aortas of Patients With Bicuspid Aortic Valve
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Shohreh Maleki, Flore-Anne Poujade, Otto Bergman, Jesper R. Gådin, Nancy Simon, Karin Lång, Anders Franco-Cereceda, Simon C. Body, Hanna M. Björck, and Per Eriksson
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bicuspid aortc valve ,aneurysm ,endothelial to mesenchymal transition (EndMT) ,ascending aorta ,endothelial cell (EC) ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Thoracic aortic aneurysm (TAA) is the progressive enlargement of the aorta due to destructive changes in the connective tissue of the aortic wall. Aneurysm development is silent and often first manifested by the drastic events of aortic dissection or rupture. As yet, therapeutic agents that halt or reverse the process of aortic wall deterioration are absent, and the only available therapeutic recommendation is elective prophylactic surgical intervention. Being born with a bicuspid instead of the normal tricuspid aortic valve (TAV) is a major risk factor for developing aneurysm in the ascending aorta later in life. Although the pathophysiology of the increased aneurysm susceptibility is not known, recent studies are suggestive of a transformation of aortic endothelium into a more mesenchymal state i.e., an endothelial-to-mesenchymal transition in these individuals. This process involves the loss of endothelial cell features, resulting in junction instability and enhanced vascular permeability of the ascending aorta that may lay the ground for increased aneurysm susceptibility. This finding differentiates and further emphasizes the specific characteristics of aneurysm development in individuals with a bicuspid aortic valve (BAV). This review discusses the possibility of a developmental fate shared between the aortic endothelium and aortic valves. It further speculates about the impact of aortic endothelium phenotypic shift on aneurysm development in individuals with a BAV and revisits previous studies in the light of the new findings.
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- 2019
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6. Altered DNA methylation indicates an oscillatory flow mediated epithelial-to-mesenchymal transition signature in ascending aorta of patients with bicuspid aortic valve
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Hanna M. Björck, Lei Du, Silvia Pulignani, Valentina Paloschi, Karin Lundströmer, Alexandra S. Kostina, Cecilia Österholm, Anna Malashicheva, Anna Kostareva, Arturo Evangelista, Gisela Teixidó-Tura, Shohreh Maleki, Anders Franco-Cereceda, Per Eriksson, and Mechanistic Interrogation of Bicuspid Aortic Valve associated Aortopathy (MIBAVA) Leducq Consortium
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Medicine ,Science - Abstract
Abstract Disturbed flow has been suggested to contribute to aneurysm susceptibility in bicuspid aortic valve (BAV) patients. Lately, flow has emerged as an important modulator of DNA methylation. Hear we combined global methylation analysis with in vitro studies of flow-sensitive methylation to identify biological processes associated with BAV-aortopathy and the potential contribution of flow. Biopsies from non-dilated and dilated ascending aortas were collected from BAV (n = 21) and tricuspid aortic valve (TAV) patients (n = 23). DNA methylation and gene expression was measured in aortic intima-media tissue samples, and in EA.hy926 and primary aortic endothelial cells (ECs) isolated from BAV and TAV exposed to oscillatory (±12 dynes/cm2) or laminar (12 dynes/cm2) flow. We show methylation changes related to epithelial-mesenchymal-transition (EMT) in the non-dilated BAV aorta, associated with oscillatory flow related to endocytosis. The results indicate that the flow-response in BAV ECs involves hypomethylation and increased expression of WNT/β-catenin genes, as opposed to an angiogenic profile in TAV ECs. The EMT-signature was exasperated in dilated BAV aortas. Aberrant EMT in BAV aortic walls could contribute to increased aneurysm susceptibility, and may be due to disturbed flow-exposure. Perturbations during the spatiotemporally related embryonic development of ascending aorta and semilunar valves can however not be excluded.
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- 2018
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7. Elevated Glucagon-like Peptide-1 and a Th2 Shift May Support Reduced Prevalence of Thoracic Aortic Aneurysm in Patients with Diabetes
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Stelia Ntika, Harshitha Jois, Karin Lång, Christian Olsson, Anders Franco-Cereceda, Hanna M. Björck, and Camilla Krizhanovskii
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aneurysm ,type 2 diabetes ,glucagon-like peptide-1 ,inflammation ,cytokines ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Glucagon-like peptide-1 (GLP-1) regulates processes involved in the pathophysiology of thoracic aortic aneurysms (TAAs), including inflammation, while protecting against aortic aneurysms in animal models. Type 2 diabetes (T2D) involves altered GLP-1 signaling due to pathology and/or therapy and is associated with reduced prevalence of TAAs. We aimed to assess whether T2D alters the inflammatory profile/proteolytic activity, possible correlations to elevated fasting GLP-1 (F-GLP-1), and its relevance for TAA. F-GLP-1, pro-inflammatory T helper 1 (Th1) cytokines, Th2 cytokines, C-reactive protein, and matrix metalloproteinase-2 activity (MMP-2) were analyzed in surgical patients with aortic valve pathology with/without T2D and without T2D but with TAA. Patients with T2D displayed an increase in the relative systemic expression of interleukin 6 and tumor necrosis factor α and a clear trend towards reduced levels of interferon γ (IFNγ). In addition, a positive association between GLP-1 and the plasma interleukin 4 (IL-4)/IFNγ ratio was detected. TAA was associated with significantly lower plasma levels of the Th2 cytokines IL-4 and interleukin 5. Plasma MMP-2 activity did not differ between groups. We conclude that T2D involved a Th2 shift, which associates with elevated F-GLP-1 and may—considering Th1 bias in TAA—contribute to reduced prevalence of TAA in T2D.
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- 2021
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8. Bicuspid aortic valve aortopathy is characterized by embryonic epithelial to mesenchymal transition and endothelial instability
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David Freiholtz, Otto Bergman, Karin Lång, Flore-Anne Poujade, Valentina Paloschi, Carl Granath, Jan H. N. Lindeman, Christian Olsson, Anders Franco-Cereceda, Per Eriksson, and Hanna M. Björck
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Drug Discovery ,Molecular Medicine ,Genetics (clinical) - Abstract
Abstract Bicuspid aortic valve (BAV) is the most common congenital heart malformation frequently associated with ascending aortic aneurysm (AscAA). Epithelial to mesenchymal transition (EMT) may play a role in BAV-associated AscAA. The aim of the study was to investigate the type of EMT associated with BAV aortopathy using patients with a tricuspid aortic valve (TAV) as a reference. The state of the endothelium was further evaluated. Aortic biopsies were taken from patients undergoing open-heart surgery. Aortic intima/media miRNA and gene expression was analyzed using Affymetrix human transcriptomic array. Histological staining assessed structure, localization, and protein expression. Migration/proliferation was assessed using ORIS migration assay. We show different EMT types associated with BAV and TAV AscAA. Specifically, in BAV-associated aortopathy, EMT genes related to endocardial cushion formation were enriched. Further, BAV vascular smooth muscle cells were less proliferative and migratory. In contrast, TAV aneurysmal aortas displayed a fibrotic EMT phenotype with medial degenerative insults. Further, non-dilated BAV aortas showed a lower miRNA-200c-associated endothelial basement membrane LAMC1 expression and lower CD31 expression, accompanied by increased endothelial permeability indicated by increased albumin infiltration. Embryonic EMT is a characteristic of BAV aortopathy, associated with endothelial instability and vascular permeability of the non-dilated aortic wall. Key messages Embryonic EMT is a feature of BAV-associated aortopathy. Endothelial integrity is compromised in BAV aortas prior to dilatation. Non-dilated BAV ascending aortas are more permeable than aortas of tricuspid aortic valve patients.
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- 2023
9. Syndecan-1 Expression Is Increased in the Aortic Wall of Patients with Type 2 Diabetes but Is Unrelated to Elevated Fasting Plasma Glucagon-Like Peptide-1
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Stelia Ntika, Linda M. Tracy, Anders Franco-Cereceda, Hanna M. Björck, and Camilla Krizhanovskii
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thoracic aortic aneurysm ,type 2 diabetes ,adventitia ,syndecan-1 ,glucagon-like peptide-1 ,Biology (General) ,QH301-705.5 - Abstract
A reduced prevalence of a thoracic aortic aneurysm (thoracic AA) is observed in type 2 diabetes (T2D). Glucagon-like peptide-1 (GLP-1)/GLP-1-based anti-diabetic therapy has indicated protective effects in thoracic AA and regulates the processes controlling the vascular tissue expression of Syndecan-1 (Sdc-1). Sdc-1 expression on macrophages infiltrating the aortic tissue contributes to a counter-regulatory response to thoracic AA formation in animal models through the interplay with inflammation/proteolytic activity. We hypothesized that elevated fasting plasma GLP-1 (fpGLP-1) increases the aortic Sdc-1 expression in T2D, which may contribute to a reduced prevalence of thoracic AA. Consequently, we determined whether T2D/thoracic AA associates with an altered Sdc-1 expression in the aortic tissue and the possible associations with fpGLP-1 and inflammation/proteolytic activity. From a cohort of surgical patients with an aortic valve pathology, we compared different disease groups (T2D/thoracic AA) with the same sub-cohort group of controls (patients without T2D and thoracic AA). The MMP-2 activity and Sdc-1, GLP-1R and CD68 expression were analyzed in the aortic tissue. GLP-1, Sdc-1 and cytokines were analyzed in the plasma. The aortic Sdc-1 expression was increased in T2D patients but did not correlate with fpGLP-1. Thoracic AA was associated with an increased aortic expression of Sdc-1 and the macrophage marker CD68. CD68 was not detected in T2D. In conclusion, an increased aortic Sdc-1 expression may contribute to a reduced prevalence of thoracic AA in T2D.
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- 2021
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10. Proteomic analysis of 92 circulating proteins and their effects in cardiometabolic diseases
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Corinne Carland, Grace Png, Anders Malarstig, Pik Fang Kho, Stefan Gustafsson, Karl Michaelsson, Lars Lind, Emmanouil Tsafantakis, Maria Karaleftheri, George Dedoussis, Anna Ramisch, Erin Macdonald-Dunlop, Lucija Klaric, Peter K. Joshi, Yan Chen, Hanna M. Björck, Per Eriksson, Julia Carrasco-Zanini, Eleanor Wheeler, Karsten Suhre, Arthur Gilly, Eleftheria Zeggini, Ana Viñuela, Emmanouil T. Dermitzakis, James F. Wilson, Claudia Langenberg, Gaurav Thareja, Anna Halama, Frank Schmidt, SCALLOP Consortium, Daniela Zanetti, and Themistocles Assimes
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Background: Human plasma contains a wide variety of circulating proteins. These proteins can be important clinical biomarkers in disease and also possible drug targets. Large scale genomics studies of circulating proteins can identify genetic variants that lead to relative protein abundance. Methods: We conducted a meta-analysis on genome-wide association studies of autosomal chromosomes in 22,997 individuals of primarily European ancestry across 12 cohorts to identify protein quantitative trait loci (pQTL) for 92 cardiometabolic associated plasma proteins. Results: We identified 503 (337 cis and 166 trans) conditionally independent pQTLs, including several novel variants not reported in the literature. We conducted a sex-stratified analysis and found that 118 (23.5%) of pQTLs demonstrated heterogeneity between sexes. The direction of effect was preserved but there were differences in effect size and significance. Additionally, we annotate trans-pQTLs with nearest genes and report plausible biological relationships. Using Mendelian randomization, we identified causal associations for 18 proteins across 19 phenotypes, of which 10 have additional genetic colocalization evidence. We highlight proteins associated with a constellation of cardiometabolic traits including angiopoietin-related protein 7 (ANGPTL7) and Semaphorin 3F (SEMA3F). Conclusion: Through large-scale analysis of protein quantitative trait loci, we provide a comprehensive overview of common variants associated with plasma proteins. We highlight possible biological relationships which may serve as a basis for further investigation into possible causal roles in cardiometabolic diseases.
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- 2023
11. The junctional mechanosensor AmotL2 regulates YAP promotor accessibility
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Aarren J. Mannion, Honglei Zhao, Yuanyuan Zhang, Ylva von Wright, Otto Bergman, Hanna M. Björck, Pipsa Saharinen, and Lars Holmgren
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Endothelial cells (ECs) are constantly exposed to mechanical forces in the form of fluid shear stress, extracellular stiffness, and cyclic strain. How these forces are sensed by ECs remains an understudied aspect in the homeostatic regulation of the circulatory system. Angiomotin-like 2 (AmotL2) is localised to EC junctions and is required for alignment and actin reorganisation under conditions of high shear stress. Here we show that AmotL2 crucially regulates transcription and promotor activity of the YAP gene. Functionally, density-dependent proliferation of ECsin vitroand proliferation of a subpopulation of ECs within the inner aortic arch, were both reliant on AmotL2 and Yap/Taz endothelial expressionin vivo. Mechanistically, depletion of AmotL2 led to altered nuclear morphology, chromatin accessibility and suppression of YAP-promotor activity through increased H3K27me3 mediated by the polycromb repressive complex component EZH2. Our data describe a previously unknown role for junctional mechanotransduction in shaping the epigenetic landscape and transcriptional regulation of YAP in vascular homeostasis.
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- 2023
12. Focused update on patients treated with the nellix endovascular aneurysm sealing (EVAS) system from the european society for vascular surgery (ESVS) abdominal aortic aneurysm clinical practice guidelines
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Jonathan R. Boyle, Nikolaos Tsilimparis, Isabelle Van Herzeele, Anders Wanhainen, F. Bastos Gonçalves, S. Bellmunt, X. Berard, M. D’Oria, C. Fernandez, C. Karkos, A. Kazimierczak, M. Koelemay, T. Kölbel, K. Mani, G. Melissano, J. Powell, S. Trimarchi, G. Antoniou, R. Coscas, N. Dias, P. Kolh, S. Lepidi, B. Mees, T. Resch, J.B. Ricco, R. Tulamo, C. Twine, and M. Björck
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Endovascular Aneurysm Sealing ,Kardiologi ,Endoleak ,Kirurgi ,Abdominal aortic aneurysm ,Surgery ,Cardiac and Cardiovascular Systems ,Guidelines ,Cardiology and Cardiovascular Medicine ,Nellix ,EVAS - Abstract
Objective: After alerts on EndoVascular Aneurysm Seal (EVAS) failure were raised, the European Society for Vascular Surgery (ESVS) Abdominal Aortic Aneurysm (AAA) Clinical Practice Guidelines Writing Committee (WC) initiated a task force with the aim to provide guidance on surveillance and management of patients with implanted EVAS devices.Methods: Based on a scoping review of risk for late serious aortic-related adverse events in patients treated with EVAS for AAA, the ESVS AAA Guidelines WC agreed on recommendations graded according to the European Society of Cardiology (ESC) grading system.Results: EVAS has a very high incidence of late endograft migration resulting in proximal type 1 endoleak with risk of rupture, requiring open conversion with device explantation. The reported mortality rate for elective explantation varies between 0% and 14%, while acute conversion for rupture has a very dismal prognosis with a 67 -75% mortality rate.Conclusion: It is recommended that all patients in whom a Nellix device has been implanted should be identified, properly informed, and enrolled in enhanced surveillance. If device failure is detected, early elective device explantation should be considered in surgically fit patients. The authors, on behalf of the ESVS AAA Guidelines Writing Committee and the ESVS Guidelines Steering Committee.
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- 2023
13. Metformin therapy is not associated with the lower prevalence of ascending aortic aneurysm in diabetic patients
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Christian Olsson, Hanna M. Björck, Anders Franco-Cereceda, Stelia Ntika, and Maxime Vignac
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Systemic inflammation ,Gastroenterology ,Mice ,Aortic aneurysm ,Aneurysm ,Internal medicine ,Diabetes mellitus ,medicine.artery ,Ascending aorta ,Diabetes Mellitus ,Prevalence ,medicine ,Animals ,Humans ,Retrospective Studies ,business.industry ,General Medicine ,Odds ratio ,medicine.disease ,Metformin ,Abdominal aortic aneurysm ,Aortic Aneurysm ,Aortic Valve ,Surgery ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Aortic Aneurysm, Abdominal ,medicine.drug - Abstract
OBJECTIVES Metformin therapy has previously been associated with reduced abdominal aortic aneurysm growth rate in diabetic patients and shown to suppress the formation and progression of abdominal aortic aneurysm in normoglycemic mice. Here, we investigated the association between Metformin treatment and prevalence of aneurysm in the ascending aorta (AscAA). METHODS A total of 734 patients undergoing open-heart surgery for AscAA and/or aortic valve disease were studied. Diabetes status and medication use were self-reported by the patients in a systematic questionnaire. Aortic dilatation was defined as an aortic root or ascending aortic diameter ≥4.0 cm. High-sensitivity C-reactive protein levels were assessed as a measure of systemic inflammation. RESULTS We could confirm the inverse association between diabetes and AscAA prevalence (16% vs 43.9%, for diabetic and non-diabetic patients, respectively; Odds ratio 0.243; 95% CI, 0.129–0.460, P CONCLUSIONS Our data do not support a protective effect of Metformin therapy in AscAA formation. Subj collection 161, 173
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- 2021
14. Kupffer cells dictate hepatic responses to the atherogenic dyslipidemic insult
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Sanna Hellberg, Osman Ahmed, Yuyang Zhang, Giada Di Nunzio, Hanna M Björck, Roy Francis, Linn Fagerberg, Anton Gisterå, Xueming Zhang, Jari Metso, Valentina Manfé, Yosdel Soto, Anders Franco-Cereceda, Per Eriksson, Matti Jauhiainen, Peder S. Olofsson, and Stephen G. Malin
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Apolipoprotein-B (APOB) containing lipoproteins are causative for atherosclerotic cardiovascular disease. Whether the vasculature is the initial responding site or if atherogenic-dyslipidemia effects other organs simultaneously is unknown. We set out to discover how the liver responds to a dyslipidemic insult through the creation of inducible mouse models based on human familial hypercholesterolemia mutations andin vivotracing of APOB. An acute transition to atherogenic APOB-lipoprotein plasma levels resulted in rapid accumulation of triglycerides and cholesterol in the liver. Single cell RNA-seq and flow cytometry disclosed that multiple immune cells have the ability to engulf APOB-lipoproteins. However bulk RNA-seq of the liver revealed an inflammatory Kupffer cell-specific transcriptional program that could not be activated by a western diet alone. Depletion of Kupffer cells through clodronate liposomes or CD8 T cell targeting rapidly raised plasma lipoprotein levels, indicating that these liver macrophages help restrain and buffer atherogenic lipoproteins, whilst simultaneously secreting pro-atherosclerotic factors into plasma. Our results place Kupffer cells as a key gateway in organizing systemic responses at the initiation of atherosclerosis.
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- 2022
15. Focused Update on Patients Treated with the Nellix EndoVascular Aneurysm Sealing (EVAS) System from the European Society for Vascular Surgery (ESVS) Abdominal Aortic Aneurysm Clinical Practice Guidelines
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J.R. Boyle, N. Tsilimparis, I. Van Herzeele, A. Wanhainen, F. Bastos Gonçalves, S. Bellmunt, X. Berard, M. D’Oria, C. Fernandez, C. Karkos, A. Kazimierczak, M. Koelemay, T. Kölbel, K. Mani, G. Melissano, J. Powell, S. Trimarchi, G. Antoniou, R. Coscas, N. Dias, P. Kolh, S. Lepidi, B. Mees, T. Resch, J.B. Ricco, R. Tulamo, C. Twine, and M. Björck
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Surgery ,Cardiology and Cardiovascular Medicine - Published
- 2023
16. Corrigendum: Candidate Gene Resequencing in a Large Bicuspid Aortic Valve-Associated Thoracic Aortic Aneurysm Cohort: SMAD6 as an Important Contributor
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Elisabeth Gillis, Ajay A. Kumar, Ilse Luyckx, Christoph Preuss, Elyssa Cannaerts, Gerarda van de Beek, Björn Wieschendorf, Maaike Alaerts, Nikhita Bolar, Geert Vandeweyer, Josephina Meester, Florian Wünnemann, Russell A. Gould, Rustam Zhurayev, Dmytro Zerbino, Salah A. Mohamed, Seema Mital, Luc Mertens, Hanna M. Björck, Anders Franco-Cereceda, Andrew S. McCallion, Lut Van Laer, Judith M. A. Verhagen, Ingrid M. B. H. van de Laar, Marja W. Wessels, Emmanuel Messas, Guillaume Goudot, Michaela Nemcikova, Alice Krebsova, Marlies Kempers, Simone Salemink, Toon Duijnhouwer, Xavier Jeunemaitre, Juliette Albuisson, Per Eriksson, Gregor Andelfinger, Harry C. Dietz, Aline Verstraeten, Bart L. Loeys, and Mibava Leducq Consortium
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bicuspid aortic valve ,thoracic aortic aneurysm ,SMAD6 ,targeted gene panel ,variant burden test ,Physiology ,QP1-981 - Published
- 2017
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17. Acknowledgment of Reviewers
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F. Dick and M. Björck
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Surgery ,Cardiology and Cardiovascular Medicine - Published
- 2021
18. Candidate Gene Resequencing in a Large Bicuspid Aortic Valve-Associated Thoracic Aortic Aneurysm Cohort: SMAD6 as an Important Contributor
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Elisabeth Gillis, Ajay A. Kumar, Ilse Luyckx, Christoph Preuss, Elyssa Cannaerts, Gerarda van de Beek, Björn Wieschendorf, Maaike Alaerts, Nikhita Bolar, Geert Vandeweyer, Josephina Meester, Florian Wünnemann, Russell A. Gould, Rustam Zhurayev, Dmytro Zerbino, Salah A. Mohamed, Seema Mital, Luc Mertens, Hanna M. Björck, Anders Franco-Cereceda, Andrew S. McCallion, Lut Van Laer, Judith M. A. Verhagen, Ingrid M. B. H. van de Laar, Marja W. Wessels, Emmanuel Messas, Guillaume Goudot, Michaela Nemcikova, Alice Krebsova, Marlies Kempers, Simone Salemink, Toon Duijnhouwer, Xavier Jeunemaitre, Juliette Albuisson, Per Eriksson, Gregor Andelfinger, Harry C. Dietz, Aline Verstraeten, Bart L. Loeys, and Mibava Leducq Consortium
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bicuspid aortic valve ,thoracic aortic aneurysm ,SMAD6 ,targeted gene panel ,variant burden test ,Physiology ,QP1-981 - Abstract
Bicuspid aortic valve (BAV) is the most common congenital heart defect. Although many BAV patients remain asymptomatic, at least 20% develop thoracic aortic aneurysm (TAA). Historically, BAV-related TAA was considered as a hemodynamic consequence of the valve defect. Multiple lines of evidence currently suggest that genetic determinants contribute to the pathogenesis of both BAV and TAA in affected individuals. Despite high heritability, only very few genes have been linked to BAV or BAV/TAA, such as NOTCH1, SMAD6, and MAT2A. Moreover, they only explain a minority of patients. Other candidate genes have been suggested based on the presence of BAV in knockout mouse models (e.g., GATA5, NOS3) or in syndromic (e.g., TGFBR1/2, TGFB2/3) or non-syndromic (e.g., ACTA2) TAA forms. We hypothesized that rare genetic variants in these genes may be enriched in patients presenting with both BAV and TAA. We performed targeted resequencing of 22 candidate genes using Haloplex target enrichment in a strictly defined BAV/TAA cohort (n = 441; BAV in addition to an aortic root or ascendens diameter ≥ 4.0 cm in adults, or a Z-score ≥ 3 in children) and in a collection of healthy controls with normal echocardiographic evaluation (n = 183). After additional burden analysis against the Exome Aggregation Consortium database, the strongest candidate susceptibility gene was SMAD6 (p = 0.002), with 2.5% (n = 11) of BAV/TAA patients harboring causal variants, including two nonsense, one in-frame deletion and two frameshift mutations. All six missense mutations were located in the functionally important MH1 and MH2 domains. In conclusion, we report a significant contribution of SMAD6 mutations to the etiology of the BAV/TAA phenotype.
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- 2017
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19. Factors influencing the fascial closure rate after open abdomen treatment : Results from the European Hernia Society (EuraHS) Registry Surgical technique matters
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A G, Willms, R, Schwab, M W, von Websky, F, Berrevoet, D, Tartaglia, K, Sörelius, R H, Fortelny, M, Björck, T, Monchal, F, Brennfleck, D, Bulian, C, Beltzer, C T, Germer, J F, Lock, and A, Vanlander
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Damage control ,MESH ,medicine.medical_specialty ,Burst abdomen ,Hernia ,Abdominal compartment syndrome ,DELAYED CLOSURE ,Peritonitis ,TEMPORARY ABDOMINAL CLOSURE ,THERAPY ,compartment syndrome ,Abdominal trauma ,Fascial closure ,NPWT ,Open abdomen ,VAC ,Abdomen ,CONSENSUS DEFINITIONS ,medicine ,Medicine and Health Sciences ,Humans ,Abdominal ,ddc:610 ,Registries ,Herniorrhaphy ,business.industry ,Kirurgi ,ASSISTED WOUND CLOSURE ,TRACTION ,Abdominal Wound Closure Techniques ,Odds ratio ,medicine.disease ,DAMAGE CONTROL ,Surgery ,Fasciotomy ,Clinical trial ,body regions ,SEPTIC PATIENTS ,VACUUM ,business ,Negative-Pressure Wound Therapy ,Abdominal surgery - Abstract
Purpose Definitive fascial closure is an essential treatment objective after open abdomen treatment and mitigates morbidity and mortality. There is a paucity of evidence on factors that promote or prevent definitive fascial closure. Methods A multi-center multivariable analysis of data from the Open Abdomen Route of the European Hernia Society included all cases between 1 May 2015 and 31 December 2019. Different treatment elements, i.e. the use of a visceral protective layer, negative-pressure wound therapy and dynamic closure techniques, as well as patient characteristics were included in the multivariable analysis. The study was registered in the International Clinical Trials Registry Platform via the German Registry for Clinical Trials (DRK00021719). Results Data were included from 630 patients from eleven surgical departments in six European countries. Indications for OAT were peritonitis (46%), abdominal compartment syndrome (20.5%), burst abdomen (11.3%), abdominal trauma (9%), and other conditions (13.2%). The overall definitive fascial closure rate was 57.5% in the intention-to-treat analysis and 71% in the per-protocol analysis. The multivariable analysis showed a positive correlation of negative-pressure wound therapy (odds ratio: 2.496, p p p = 0.029) and the number of surgical procedures before OAT (odds ratio: 0.740, p = 0.005) with DFC. Conclusion The clinical course and prognosis of open abdomen treatment can significantly be improved by the use of treatment elements such as negative-pressure wound therapy and dynamic closure techniques, which are associated with definitive fascial closure.
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- 2022
20. Valve disease and aortopathy associations of bicuspid aortic valve phenotypes differ between men and women
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Salah A. Mohamed, Anders Franco-Cereceda, Carl Granath, Hanna M. Björck, Michael Grattan, Christian Olsson, and Luc Mertens
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Male ,medicine.medical_specialty ,Aortic Diseases ,aortic valve stenosis ,Aorta, Thoracic ,Global Health ,Risk Assessment ,aortic valve insufficiency ,Aortic aneurysm ,Sex Factors ,Bicuspid aortic valve ,Bicuspid Aortic Valve Disease ,Internal medicine ,Epidemiology ,medicine ,Humans ,Diseases of the circulatory (Cardiovascular) system ,Sex Distribution ,Retrospective Studies ,business.industry ,Incidence ,congenital ,Aortic and Vascular Disease ,Middle Aged ,Aortic Valve Insufficiency ,medicine.disease ,Phenotype ,Stenosis ,Cross-Sectional Studies ,Echocardiography ,Aortic valve stenosis ,RC666-701 ,heart defects ,Cardiology ,epidemiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,aortic aneurysm ,Valve disease ,Follow-Up Studies - Abstract
ObjectiveDetermine whether associations between bicuspid aortic valve (BAV) phenotypes, valve disease and aortopathy differ between sexes.Methods1045 patients with BAV (76.0% men, n=794) from two surgical centres were included in this cross-sectional study. Valve phenotype was classified intraoperatively as right–left (RL), right-non-coronary (RN), left-non-coronary (LN) or 2-sinus BAV. Echocardiography was used to determine type and degree of valve disease, and aortic dimensions. Aortic dilatation was defined as diameter ≥4.5 cm.ResultsRL was the most common phenotype (73.6%), followed by RN (16.2%), 2-sinus BAV (9.2%) and LN (1.1%), with no difference in phenotype distribution between men and women (p=0.634). Aortic valve insufficiency (AI) prevalence differed significantly with valve phenotype in men (p=0.047), with RL and LN having the highest prevalence (34.1% and 44.0%, respectively). In women, RN had a higher proportion of AI than RL (21.3% vs 7.3%, p=0.017). Men with RL had larger root dimensions, in particular at the sinus (mean difference 0.24 cm compared with RN, p=0.002). Men with 2-sinus BAV had the highest prevalence of root phenotype dilatation (7.0%, other phenotypes ≤2.3%, p=0.031), whereas women with 2-sinus BAV did not have root dilatation and smaller sinus dimensions (mean difference: 0.35 cm compared with RL, p=0.021). Aortic root segments were larger in men with AI compared with aortic stenosis (sinus mean difference: 0.40 cm, pConclusionsThere are significant sex differences in clinical associations of BAV phenotypes, which should be considered in further studies on the role of phenotypes in individualised patient management.
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- 2021
21. Clinical Classifiers to Identify Ascending Aortic Dilatation in Patients With Bicuspid Versus Tricuspid Aortic Valves
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Bamba Gaye, Maxime Vignac, Jesper R. Gådin, Magalie Ladouceur, Kenneth Caidahl, Christian Olsson, Anders Franco-Cereceda, Per Eriksson, and Hanna M Björck
- Abstract
Objective: We aimed to develop clinical classifiers to identify prevalent ascending aortic dilatation in patients with BAV and tricuspid aortic valve (TAV). Methods: This study included BAV (n=543) and TAV (n=491) patients with aortic valve disease and/or ascending aortic dilatation but devoid of coronary artery disease undergoing cardiothoracic surgery. We applied machine learning algorithms and classic logistic regression models, using multiple variable selection methodologies to identify predictors of high risk of ascending aortic dilatation (ascending aorta with a diameter above 40 mm). Analyses included comprehensive multidimensional data (i.e., valve morphology, clinical data, family history of cardiovascular diseases, prevalent diseases, demographic, lifestyle and medication). Results: BAV patients were younger (60.4±12.4 years) than TAV patients (70.4±9.1 years), and had a higher frequency of aortic dilatation (45.3% vs. 28.9% for BAV and TAV, respectively. PConclusions: Cardiovascular risk profiles appear to be more predictive of aortopathy in TAV patients than in patients with BAV. This adds evidence to the fact that BAV- and TAV-associated aortopathy involve different pathways to aneurysm formation and highlights the need for specific aneurysm preventions in these patients. Further, our results highlight that machine learning approaches do not outperform classical prediction methods in addressing complex interactions and non-linear relations between variables.
- Published
- 2021
22. Sex Differences in Aortopathy and Valve Diseases Among Patients Undergoing Cardiac Surgical Procedure
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Maxime Vignac, Hanna M. Björck, Christian Olsson, Maria J. Eriksson, Xavier Jouven, Erin D. Michos, Anders Franco-Cereceda, Per Eriksson, and Bamba Gaye
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Pulmonary and Respiratory Medicine ,Male ,Endocarditis ,Heart Valve Diseases ,Aortic Valve Stenosis ,Aortic Aneurysm ,Bicuspid Aortic Valve Disease ,Aortic Valve ,Humans ,Surgery ,Female ,Cardiac Surgical Procedures ,Cardiology and Cardiovascular Medicine ,Retrospective Studies - Abstract
We aimed to study sex differences in aortopathy and valve disease among patients undergoing aortic valve replacement and/or surgical procedure for ascending aortic aneurysm and assess whether differences are specific for patients with bicuspid aortic valve (BAV) compared with patients with tricuspid aortic valve.We used a single-center and observational cohort including 1045 patients undergoing elective open heart surgical procedure for aortic valve disease and/or ascending aortic aneurysm at the Karolinska Hospital (Stockholm, Sweden).Women (33.0%) were older than men (mean [SD]; 67.9 [11] years vs 62.5 [13] years for men; P.001). No significant sex difference in prevalence of ascending aortic aneurysm was found according to absolute measures (P = .19); however, women had a greater dilation of the ascending aorta when normalized for body surface area (mean, 21.8 [SD, 6.3] mm/mIn this large study of patients undergoing cardiac surgical procedure, we found a greater degree of aortic dilation in women compared with men, suggesting a need for earlier monitoring of women. Moreover, women with BAV had a significantly higher prevalence of aortic stenosis compared with men. These results describe the aorta and valvular characteristics of patients by sex and provide guidance regarding which patients might benefit from closer surveillance.
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- 2021
23. European Society for Vascular Surgery Clinical Practice Guideline Development Scheme: An Overview of Evidence Quality Assessment Methods, Evidence to Decision Frameworks, and Reporting Standards in Guideline Development
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G.A. Antoniou, F. Bastos Gonçalves, M. Björck, N. Chakfé, R. Coscas, N.V. Dias, F. Dick, S.K. Kakkos, B.M.E. Mees, T. Resch, S. Trimarchi, R. Tulamo, C.P. Twine, F. Vermassen, A. Wanhainen, and P. Kolh
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Surgery ,610 Medicine & health ,Cardiology and Cardiovascular Medicine - Abstract
OBJECTIVE A structured and transparent approach is instrumental in translating research evidence to health recommendations and evidence informed clinical decisions. The aim was to conduct an overview and analysis of principles and methodologies for health guideline development. METHODS A literature review on methodologies, strategies, and fundamental steps in the process of guideline development was performed. The clinical practice guideline development process and methodology adopted by the European Society for Vascular Surgery are also presented. RESULTS Sophisticated methodologies for health guideline development are being applied increasingly by national and international organisations. Their overarching principle is a systematic, structured, transparent, and iterative process that is aimed at making well informed healthcare choices. Critical steps in guideline development include the assessment of the certainty of the body of evidence; evidence to decision frameworks; and guideline reporting. The goal of strength of evidence assessments is to provide well reasoned judgements about the guideline developers' confidence in study findings, and several evidence hierarchy schemes and evidence rating systems have been described for this purpose. Evidence to decision frameworks help guideline developers and users conceptualise and interpret the construct of the quality of the body of evidence. The most widely used evidence to decision frameworks are those developed by the GRADE Working Group and the WHO-INTEGRATE, and are structured into three distinct components: background; assessment; and conclusions. Health guideline reporting tools are employed to ensure methodological rigour and transparency in guideline development. Such reporting instruments include the AGREE II and RIGHT, with the former being used for guideline development and appraisal, as well as reporting. CONCLUSION This guide will help guideline developers/expert panels enhance their methodology, and patients/clinicians/policymakers interpret guideline recommendations and put them in context. This document may be a useful methodological summary for health guideline development by other societies and organisations.
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- 2022
24. Syndecan-1 Expression Is Increased in the Aortic Wall of Patients with Type 2 Diabetes but Is Unrelated to Elevated Fasting Plasma Glucagon-Like Peptide-1
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Anders Franco-Cereceda, Camilla Krizhanovskii, Hanna M. Björck, Stelia Ntika, and Linda M. Tracy
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Aortic valve ,medicine.medical_specialty ,endocrine system ,QH301-705.5 ,thoracic aortic aneurysm ,Medicine (miscellaneous) ,Inflammation ,Type 2 diabetes ,030204 cardiovascular system & hematology ,Thoracic aortic aneurysm ,General Biochemistry, Genetics and Molecular Biology ,Article ,Syndecan 1 ,adventitia ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Adventitia ,medicine ,Biology (General) ,business.industry ,CD68 ,syndecan-1 ,medicine.disease ,Glucagon-like peptide-1 ,medicine.anatomical_structure ,Endocrinology ,glucagon-like peptide-1 ,030220 oncology & carcinogenesis ,type 2 diabetes ,medicine.symptom ,business - Abstract
A reduced prevalence of a thoracic aortic aneurysm (thoracic AA) is observed in type 2 diabetes (T2D). Glucagon-like peptide-1 (GLP-1)/GLP-1-based anti-diabetic therapy has indicated protective effects in thoracic AA and regulates the processes controlling the vascular tissue expression of Syndecan-1 (Sdc-1). Sdc-1 expression on macrophages infiltrating the aortic tissue contributes to a counter-regulatory response to thoracic AA formation in animal models through the interplay with inflammation/proteolytic activity. We hypothesized that elevated fasting plasma GLP-1 (fpGLP-1) increases the aortic Sdc-1 expression in T2D, which may contribute to a reduced prevalence of thoracic AA. Consequently, we determined whether T2D/thoracic AA associates with an altered Sdc-1 expression in the aortic tissue and the possible associations with fpGLP-1 and inflammation/proteolytic activity. From a cohort of surgical patients with an aortic valve pathology, we compared different disease groups (T2D/thoracic AA) with the same sub-cohort group of controls (patients without T2D and thoracic AA). The MMP-2 activity and Sdc-1, GLP-1R and CD68 expression were analyzed in the aortic tissue. GLP-1, Sdc-1 and cytokines were analyzed in the plasma. The aortic Sdc-1 expression was increased in T2D patients but did not correlate with fpGLP-1. Thoracic AA was associated with an increased aortic expression of Sdc-1 and the macrophage marker CD68. CD68 was not detected in T2D. In conclusion, an increased aortic Sdc-1 expression may contribute to a reduced prevalence of thoracic AA in T2D.
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- 2021
25. Effect of Carotid Endarterectomy on 20 Year Incidence of Recorded Dementia: A Randomised Trial
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A. Halliday, M. Sneade, M. Björck, S.T. Pendlebury, R. Bulbulia, S. Parish, R. Llewellyn-Bennett, H. Pan, W. Whiteley, and A. Gottsäter
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Surgery ,Cardiology and Cardiovascular Medicine - Published
- 2022
26. Hyperglycemia Induces Myocardial Dysfunction via Epigenetic Regulation of JunD
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Shafaat Hussain, Kenneth Caidahl, Thomas F. Lüscher, Francesco Cosentino, Francesco Paneni, John Pernow, Lars Lund, Christos Gkolfos, Alexander Akhmedov, Shafeeq A. Mohammed, Rosa Suades, Abdul Waheed Khan, Camilla Hage, Sarah Costantino, and Hanna M. Björck
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0301 basic medicine ,Male ,Physiology ,Diabetic Cardiomyopathies ,Proto-Oncogene Proteins c-jun ,Protein subunit ,030204 cardiovascular system & hematology ,Proto-Oncogene Mas ,Epigenesis, Genetic ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Superoxide Dismutase-1 ,Diabetes mellitus ,Proto-Oncogene Proteins ,microRNA ,medicine ,Animals ,Humans ,Epigenetics ,Transcription factor ,chemistry.chemical_classification ,Reactive oxygen species ,Activator (genetics) ,business.industry ,Myocardium ,NF-kappa B ,DNA Methylation ,medicine.disease ,Histone Code ,Mice, Inbred C57BL ,MicroRNAs ,030104 developmental biology ,chemistry ,NADPH Oxidase 4 ,Heart failure ,Hyperglycemia ,NADPH Oxidase 2 ,Cancer research ,Cardiology and Cardiovascular Medicine ,business ,Reactive Oxygen Species - Abstract
Rationale: Hyperglycemia -induced reactive oxygen species are key mediators of cardiac dysfunction. JunD (Jund proto-oncogene subunit), a member of the AP-1 (activator protein-1) family of transcription factors, is emerging as a major gatekeeper against oxidative stress. However, its contribution to redox state and inflammation in the diabetic heart remains to be elucidated. Objective: The present study investigates the role of JunD in hyperglycemia-induced and reactive oxygen species–driven myocardial dysfunction. Methods and Results: JunD mRNA and protein expression were reduced in the myocardium of mice with streptozotocin-induced diabetes mellitus as compared to controls. JunD downregulation was associated with oxidative stress and left ventricular dysfunction assessed by electron spin resonance spectroscopy as well as conventional and 2-dimensional speckle-tracking echocardiography. Furthermore, myocardial expression of free radical scavenger superoxide dismutase 1 and aldehyde dehydrogenase 2 was reduced, whereas the NOX2 (NADPH [nicotinamide adenine dinucleotide phosphatase] oxidase subunit 2) and NOX4 (NADPH [nicotinamide adenine dinucleotide phosphatase] oxidase subunit 4) were upregulated. The redox changes were associated with increased NF-κB (nuclear factor kappa B) binding activity and expression of inflammatory mediators. Interestingly, mice with cardiac-specific overexpression of JunD via the α MHC (α- myosin heavy chain) promoter (α MHC JunD tg ) were protected against hyperglycemia-induced cardiac dysfunction. We also showed that JunD was epigenetically regulated by promoter hypermethylation, post-translational modification of histone marks, and translational repression by miRNA (microRNA)-673/menin. Reduced JunD mRNA and protein expression were confirmed in left ventricular specimens obtained from patients with type 2 diabetes mellitus as compared to nondiabetic subjects. Conclusions: Here, we show that a complex epigenetic machinery involving DNA methylation, histone modifications, and microRNAs mediates hyperglycemia-induced JunD downregulation and myocardial dysfunction in experimental and human diabetes mellitus. Our results pave the way for tissue-specific therapeutic modulation of JunD to prevent diabetic cardiomyopathy.
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- 2020
27. Characterization of Laminins in Healthy Human Aortic Valves and a Modified Decellularized Rat Scaffold
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Hanna M. Björck, Kim Olesen, Karl-Henrik Grinnemo, Sergey Rodin, Cecilia Österholm, Hunter Noren, Carl Granath, and Nancy Simon
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Scaffold ,Pathology ,medicine.medical_specialty ,extracellular matrix ,General Biochemistry, Genetics and Molecular Biology ,Extracellular matrix ,Tissue engineering ,laminin ,Laminin ,medicine ,Cardiac and Cardiovascular Systems ,Original Research Article ,Prosthetic valve ,Decellularization ,Kardiologi ,biology ,business.industry ,Kirurgi ,food and beverages ,medicine.disease ,Aortic valve stenosis ,tissue engineering ,biology.protein ,Surgery ,business ,heart valves - Abstract
Aortic valve stenosis is one of the most common cardiovascular diseases in western countries and can only be treated by replacement with a prosthetic valve. Tissue engineering is an emerging and promising treatment option, but in-depth knowledge about the microstructure of native heart valves is lacking, making the development of tissue-engineered heart valves challenging. Specifically, the basement membrane (BM) of heart valves remains incompletely characterized, and decellularization protocols that preserve BM components are necessary to advance the field. This study aims to characterize laminin isoforms expressed in healthy human aortic valves and establish a small animal decellularized aortic valve scaffold for future studies of the BM in tissue engineering. Laminin isoforms were assessed by immunohistochemistry with antibodies specific for individual alpha, beta, and gamma chains. The results indicated that LN-411, LN-421, LN-511, and LN-521 are expressed in human aortic valves (n = 3), forming a continuous monolayer in the endothelial BM, whereas sparsely found in the interstitium. Similar results were seen in rat aortic valves (n = 3). Retention of laminin and other BM components, concomitantly with effective removal of cells and residual DNA, was achieved through 3 h exposure to 1% sodium dodecyl sulfate and 30 min exposure to 1% Triton X-100, followed by nuclease processing in rat aortic valves (n = 3). Our results provide crucial data on the microenvironment of valvular cells relevant for research in both tissue engineering and heart valve biology. We also describe a decellularized rat aortic valve scaffold useful for mechanistic studies on the role of the BM in heart valve regeneration. CC BY 4.0
- Published
- 2020
28. Characterization of shear-sensitive genes in the normal rat aorta identifies Hand2 as a major flow-responsive transcription factor.
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Hanna M Björck, Johan Renner, Shohreh Maleki, Siv F E Nilsson, Johan Kihlberg, Lasse Folkersen, Matts Karlsson, Tino Ebbers, Per Eriksson, and Toste Länne
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Medicine ,Science - Abstract
OBJECTIVE: Shear forces play a key role in the maintenance of vessel wall integrity. Current understanding regarding shear-dependent gene expression is mainly based on in vitro or in vivo observations with experimentally deranged shear, hence reflecting acute molecular events in relation to flow. Our objective was to combine computational fluid dynamic (CFD) simulations with global microarray analysis to study flow-dependent vessel wall biology in the aortic wall under physiological conditions. METHODS AND RESULTS: Male Wistar rats were used. Animal-specific wall shear stress (WSS) magnitude and vector direction were estimated using CFD based on aortic geometry and flow information acquired by magnetic resonance imaging. Two distinct flow pattern regions were identified in the normal rat aortic arch; the distal part of the lesser curvature being exposed to low WSS and a non-uniform vector direction, and a region along the greater curvature being subjected to markedly higher levels of WSS and a uniform vector direction. Microarray analysis identified numerous novel mechanosensitive genes, including Trpc4 and Fgf12, and confirmed well-known ones, e.g. Klf2 and Nrf2. Gene ontology analysis revealed an over-representation of genes involved in transcriptional regulation. The most differentially expressed gene, Hand2, is a transcription factor previously shown to be involved in extracellular matrix remodeling. HAND2 protein was endothelial specific and showed higher expression in the regions exposed to low WSS with disturbed flow. CONCLUSIONS: Microarray analysis validated the CFD-defined WSS regions in the rat aortic arch, and identified numerous novel shear-sensitive genes. Defining the functional importance of these genes in relation to atherosusceptibility may provide important insight into the understanding of vascular pathology.
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- 2012
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29. Endothelial/Epithelial Mesenchymal Transition in Ascending Aortas of Patients With Bicuspid Aortic Valve
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Jesper R. Gådin, Nancy Simon, Karin Lång, Simon C. Body, Hanna M. Björck, Shohreh Maleki, Anders Franco-Cereceda, Per Eriksson, Flore-Anne Poujade, and Otto Bergman
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0301 basic medicine ,Aortic valve ,medicine.medical_specialty ,lcsh:Diseases of the circulatory (Cardiovascular) system ,ascending aorta ,endothelial cell (EC) ,Vascular permeability ,Review ,Cardiovascular Medicine ,030204 cardiovascular system & hematology ,bicuspid aortc valve ,Thoracic aortic aneurysm ,03 medical and health sciences ,0302 clinical medicine ,Bicuspid aortic valve ,Aneurysm ,Internal medicine ,medicine.artery ,Ascending aorta ,Medicine ,endothelial to mesenchymal transition (EndMT) ,cardiovascular diseases ,Aortic dissection ,Aorta ,business.industry ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,lcsh:RC666-701 ,Cardiology ,cardiovascular system ,aneurysm ,Cardiology and Cardiovascular Medicine ,business - Abstract
Thoracic aortic aneurysm (TAA) is the progressive enlargement of the aorta due to destructive changes in the connective tissue of the aortic wall. Aneurysm development is silent and often first manifested by the drastic events of aortic dissection or rupture. As yet, therapeutic agents that halt or reverse the process of aortic wall deterioration are absent, and the only available therapeutic recommendation is elective prophylactic surgical intervention. Being born with a bicuspid instead of the normal tricuspid aortic valve (TAV) is a major risk factor for developing aneurysm in the ascending aorta later in life. Although the pathophysiology of the increased aneurysm susceptibility is not known, recent studies are suggestive of a transformation of aortic endothelium into a more mesenchymal state i.e., an endothelial-to-mesenchymal transition in these individuals. This process involves the loss of endothelial cell features, resulting in junction instability and enhanced vascular permeability of the ascending aorta that may lay the ground for increased aneurysm susceptibility. This finding differentiates and further emphasizes the specific characteristics of aneurysm development in individuals with a bicuspid aortic valve (BAV). This review discusses the possibility of a developmental fate shared between the aortic endothelium and aortic valves. It further speculates about the impact of aortic endothelium phenotypic shift on aneurysm development in individuals with a BAV and revisits previous studies in the light of the new findings.
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- 2019
30. Altered DNA methylation indicates an oscillatory flow mediated epithelial-to-mesenchymal transition signature in ascending aorta of patients with bicuspid aortic valve
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Anna Kostareva, Lei Du, Karin Lundströmer, Shohreh Maleki, Arturo Evangelista, Per Eriksson, Silvia Pulignani, Valentina Paloschi, Gisela Teixido-Tura, Anders Franco-Cereceda, Alexandra S. Kostina, Anna Malashicheva, Hanna M. Björck, Cecilia Österholm, Mechanistic Interrogation of Bicuspid Aortic Valve associated Aortopathy (MIBAVA), and Leducq Consortium
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0301 basic medicine ,Aortic valve ,Pathology ,medicine.medical_specialty ,Epithelial-Mesenchymal Transition ,Science ,Heart Valve Diseases ,Article ,03 medical and health sciences ,Aneurysm ,Bicuspid aortic valve ,Bicuspid Aortic Valve Disease ,medicine.artery ,Ascending aorta ,medicine ,Humans ,Aorta ,Multidisciplinary ,business.industry ,Muscle cell proliferation ,Endothelial Cells ,Methylation ,DNA Methylation ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Aortic Valve ,DNA methylation ,Blood Circulation ,cardiovascular system ,Medicine ,Human medicine ,Tricuspid Valve ,business ,Transcriptome ,Dilatation, Pathologic - Abstract
Disturbed flow has been suggested to contribute to aneurysm susceptibility in bicuspid aortic valve (BAV) patients. Lately, flow has emerged as an important modulator of DNA methylation. Hear we combined global methylation analysis with in vitro studies of flow-sensitive methylation to identify biological processes associated with BAV-aortopathy and the potential contribution of flow. Biopsies from non-dilated and dilated ascending aortas were collected from BAV (n = 21) and tricuspid aortic valve (TAV) patients (n = 23). DNA methylation and gene expression was measured in aortic intima-media tissue samples, and in EA.hy926 and primary aortic endothelial cells (ECs) isolated from BAV and TAV exposed to oscillatory (±12 dynes/cm2) or laminar (12 dynes/cm2) flow. We show methylation changes related to epithelial-mesenchymal-transition (EMT) in the non-dilated BAV aorta, associated with oscillatory flow related to endocytosis. The results indicate that the flow-response in BAV ECs involves hypomethylation and increased expression of WNT/β-catenin genes, as opposed to an angiogenic profile in TAV ECs. The EMT-signature was exasperated in dilated BAV aortas. Aberrant EMT in BAV aortic walls could contribute to increased aneurysm susceptibility, and may be due to disturbed flow-exposure. Perturbations during the spatiotemporally related embryonic development of ascending aorta and semilunar valves can however not be excluded.
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- 2018
31. Elevated Glucagon-like Peptide-1 and a Th2 Shift May Support Reduced Prevalence of Thoracic Aortic Aneurysm in Patients with Diabetes
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Hanna M. Björck, Stelia Ntika, Christian Olsson, Anders Franco-Cereceda, Harshitha Jois, Camilla Krizhanovskii, and Karin Lång
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Aortic valve ,endocrine system ,medicine.medical_specialty ,Inflammation ,Thoracic aortic aneurysm ,Article ,Aneurysm ,Internal medicine ,medicine ,Diseases of the circulatory (Cardiovascular) system ,Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics ,Interleukin 6 ,Interleukin 5 ,Interleukin 4 ,biology ,business.industry ,medicine.disease ,cytokines ,Pathophysiology ,medicine.anatomical_structure ,Endocrinology ,glucagon-like peptide-1 ,inflammation ,RC666-701 ,aneurysm ,biology.protein ,type 2 diabetes ,medicine.symptom ,business - Abstract
Glucagon-like peptide-1 (GLP-1) regulates processes involved in the pathophysiology of thoracic aortic aneurysms (TAAs), including inflammation, while protecting against aortic aneurysms in animal models. Type 2 diabetes (T2D) involves altered GLP-1 signaling due to pathology and/or therapy and is associated with reduced prevalence of TAAs. We aimed to assess whether T2D alters the inflammatory profile/proteolytic activity, possible correlations to elevated fasting GLP-1 (F-GLP-1), and its relevance for TAA. F-GLP-1, pro-inflammatory T helper 1 (Th1) cytokines, Th2 cytokines, C-reactive protein, and matrix metalloproteinase-2 activity (MMP-2) were analyzed in surgical patients with aortic valve pathology with/without T2D and without T2D but with TAA. Patients with T2D displayed an increase in the relative systemic expression of interleukin 6 and tumor necrosis factor α and a clear trend towards reduced levels of interferon γ (IFNγ). In addition, a positive association between GLP-1 and the plasma interleukin 4 (IL-4)/IFNγ ratio was detected. TAA was associated with significantly lower plasma levels of the Th2 cytokines IL-4 and interleukin 5. Plasma MMP-2 activity did not differ between groups. We conclude that T2D involved a Th2 shift, which associates with elevated F-GLP-1 and may—considering Th1 bias in TAA—contribute to reduced prevalence of TAA in T2D.
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- 2021
32. Editor's Choice – Management of the Diseases of Mesenteric Arteries and Veins
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M. Björck, M. Koelemay, S. Acosta, F. Bastos Goncalves, T. Kölbel, J.J. Kolkman, T. Lees, J.H. Lefevre, G. Menyhei, G. Oderich, null ESVS Guidelines Committee, P. Kolh, G.J. de Borst, N. Chakfe, S. Debus, R. Hinchliffe, S. Kakkos, I. Koncar, J. Sanddal Lindholt, M. Vega de Ceniga, F. Vermassen, F. Verzini, null Document Reviewers, B. Geelkerken, P. Gloviczki, T. Huber, and R. Naylor
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medicine.medical_specialty ,Download ,business.industry ,Task force ,General surgery ,Endovascular surgery ,030204 cardiovascular system & hematology ,030230 surgery ,Vascular surgery ,Scientific integrity ,Surgery ,Associate editor ,Clinical Practice ,03 medical and health sciences ,Mesenteric ischaemia ,0302 clinical medicine ,Medicine ,Cardiology and Cardiovascular Medicine ,business - Abstract
Dedication These guidelines are dedicated to Paola De Rango, University of Perugia, Italy. She participated very actively in the process of developing these guidelines, in particular the important chapters on chronic arterial and venous mesenteric ischaemia. Six days after the second meeting of the task force she died unexpectedly, to our great despair and loss. We honour her dedication and scientific integrity by completing these guidelines. Among many other commitments she was a very productive reviewer and an associate editor of this journal. You can read more about Paola's important contributions to science and to the vascular community in the April 2016 issue of the European Journal of Vascular and Endovascular Surgery. 1 Download : Download high-res image (56KB) Download : Download full-size image Dr Paola De Rango, July 28, 1966 – February 21, 2016
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- 2017
33. Editor's Choice – Management of Descending Thoracic Aorta Diseases
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V. Riambau, D. Böckler, J. Brunkwall, P. Cao, R. Chiesa, G. Coppi, M. Czerny, G. Fraedrich, S. Haulon, M.J. Jacobs, M.L. Lachat, F.L. Moll, C. Setacci, P.R. Taylor, M. Thompson, S. Trimarchi, H.J. Verhagen, E.L. Verhoeven, null ESVS Guidelines Committee, P. Kolh, G.J. de Borst, N. Chakfé, E.S. Debus, R.J. Hinchliffe, S. Kakkos, I. Koncar, J.S. Lindholt, M. Vega de Ceniga, F. Vermassen, F. Verzini, null Document Reviewers, J.H. Black, R. Busund, M. Björck, M. Dake, F. Dick, H. Eggebrecht, A. Evangelista, M. Grabenwöger, R. Milner, A.R. Naylor, J.-B. Ricco, H. Rousseau, and J. Schmidli
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medicine.medical_specialty ,business.industry ,Guideline ,030204 cardiovascular system & hematology ,Vascular surgery ,Surgery ,Clinical Practice ,03 medical and health sciences ,0302 clinical medicine ,medicine.artery ,cardiovascular system ,medicine ,Thoracic aorta ,030212 general & internal medicine ,Cardiology and Cardiovascular Medicine ,business - Abstract
Editor's Choice - Management of Descending Thoracic Aorta Diseases : Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS).
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- 2017
34. Temporal Trends and Management of Acute Aortic Occlusion: A 21 Year Experience
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O. Grip, A. Wanhainen, and M. Björck
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Surgery ,Cardiology and Cardiovascular Medicine - Published
- 2019
35. Abstract P112: Prediction of the Development of Aortopathy in Patients With Bicuspid Aortic Valves
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Christian Olsson, Per Eriksson, Maxime Vignac, Magalie Ladouceur, Hanna M. Björck, Anders F Cereceda, and Bamba Gaye
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medicine.medical_specialty ,education.field_of_study ,business.industry ,Population ,Ascending aorta dilatation ,Physiology (medical) ,Internal medicine ,cardiovascular system ,Cardiology ,Medicine ,In patient ,Cardiology and Cardiovascular Medicine ,business ,education - Abstract
Background: Little is known about the association between bicuspid aortic valves (BAV) and ascending aorta dilatation in the population. We aimed to firstly determine the predictors of aortopathy in BAV patients and secondly to develop a clinical classifier to predict aortopathy in a large group of individuals with bicuspid aortic valve. Method: This study includes 1041 patients (including 545 BAV patients and 506 tricuspid aortic valves (TAV) patients) aged 18 or above with aortic valve disease and/or ascending aorta dilatation but devoid of coronary artery disease and primarily not planned for another concomitant valve surgery. Aortic complications of patients were assessed at baseline. Using automated machine-learning, we applied 10-fold cross-validation logistic regression incorporating multidimensional information (i.e., valvular dysfunction, valves morphology, blood sampling, genetic data, clinical data, family history of cardiovascular diseases, prevalent diseases data, demographic characteristics, lifestyle habits data and medication). Results: Among the 545 BAV subjects (age 64.89 +/- 12 years, 68% men). The prevalence of BAV associated with aneurysm (dilatation) (BAV-D) and without aneurysm (BAV-ND) was 54.9% and 45.1% (p Conclusion: Our findings raise the issue of how to implement prevention of aortopathy in BAV patients in a clinical setting and suggest/demonstrated that cardiovascular risk profiles appear to be more predictive than valve morphology, genetic data and circulating plasma proteins.
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- 2019
36. Diagnosis and Management of Iliac Artery Endofibrosis: Results of a Delphi Consensus Study
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Jason T. Lee, R. Palfreeman, J. B. Ricco, Louis Passfield, K. Cherry, I. Spark, P. Feugier, Justin A. Roake, F. D'Abate, M. Bender, Y. Alimi, C. Edmundson, J. Beard, B. Fernandez Garcia, M. Björck, R. E. Zierler, Y. O. Schumacher, G. Schep, G. Peach, P. Abraham, O. Rouviere, Robert J. Hinchliffe, L. J. Álvarez Fernández, and H. Rimpler
- Subjects
medicine.medical_specialty ,Delphi Technique ,medicine.medical_treatment ,External iliac artery ,Disease ,030204 cardiovascular system & hematology ,Iliac Artery ,Endofibrosis ,03 medical and health sciences ,0302 clinical medicine ,medicine.artery ,Vein patch ,medicine ,Humans ,Vascular Diseases ,Sport ,Endarterectomy ,computer.programming_language ,Iliac artery ,Surgical approach ,Peripheral artery disease ,business.industry ,General surgery ,Cycling ,Fibrosis ,Natural history ,Centre for Surgical Research ,Disease Progression ,Exercise Test ,Physical therapy ,Surgery ,Cardiology and Cardiovascular Medicine ,business ,Vascular Surgical Procedures ,computer ,030217 neurology & neurosurgery ,Delphi - Abstract
Objective\ud \ud Iliac endofibrosis is a rare condition that may result in a reduction of blood flow to the lower extremity in young, otherwise healthy individuals. The data to inform everyday clinical management are weak and therefore a Delphi consensus methodology was used to explore areas of consensus and disagreement concerning the diagnosis and management of patients with suspected iliac endofibrosis.\ud Methods\ud \ud A three-round Delphi questionnaire approach was used among vascular surgeons, sports physicians, sports scientists, radiologists, and clinical vascular scientists with experience of treating this condition to explore diagnosis and clinical management issues for patients with suspected iliac artery endofibrosis. Analysis is based on 18 responses to round 2 and 14 responses to round 3, with agreement reported when 70% of respondents were in agreement.\ud Results\ud \ud Initially there was agreement on the typical symptoms at presentation and the need for an exercise test in the diagnosis. Round 3 clarified that duplex ultrasound was a useful tool in the diagnosis of endofibrosis. There was consensus on the most appropriate type of surgery (endarterectomy and vein patch) and that endovascular interventions were inadvisable. The final round helped to inform aspects of the natural history and post-operative surveillance. Progression of the disease was likely with continued exercise but cessation may prevent progression. Surveillance after surgery is generally recommended yearly with at least a clinical assessment.\ud Conclusions\ud \ud There is broad agreement about the presenting symptoms and the investigations required to confirm (or exclude) the diagnosis of iliac endofibrosis. There was consensus on the surgical approach to repair. Disagreement existed about the specific diagnostic criteria that should be applied during non-invasive testing and about post-operative care and resumption of exercise.
- Published
- 2016
37. Detection of Late Complications After Endovascular Abdominal Aortic Aneurysm Repair and Implications for Follow up Based on Retrospective Assessment of a Two Centre Cohort
- Author
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H. Baderkhan, A. Wanhainen, O. Haller, M. Björck, and K. Mani
- Subjects
Surgery ,Cardiology and Cardiovascular Medicine - Published
- 2020
38. DNA methylation age is associated with an altered hemostatic profile in a multiethnic meta-analysis
- Author
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Karl Everett, Oscar H. Franco, James S. Pankow, Sharon L.R. Kardia, Andrew D. Johnson, Erin B. Ware, Xiuqing Guo, John M. Starr, Eric Boerwinkle, Christopher J. O'Donnell, Cavin K. Ward-Caviness, Ian J. Deary, Marine Germain, Wolfgang Koenig, Christian Gieger, Paul S. de Vries, Anders Franco-Cereceda, Barbara McKnight, Petra Wolf, Nicholas L. Smith, Jennifer E. Huffman, Per Eriksson, Weihong Tang, Kerri L. Wiggins, Min A. Jhun, Abbas Dehghan, Holger Prokisch, Gonneke Willemsen, Jenny van Dongen, Dorret I. Boomsma, Jennifer A. Smith, Wei Zhao, Joyce B. J. van Meurs, Alanna C. Morrison, Annette Peters, Daniel Levy, Melanie Waldenberger, Nona Sotoodenia, Nicholas S. Roetker, Philip S. Wells, Bruce M. Psaty, Pierre-Emmanuel Morange, Hanna M. Björck, André G. Uitterlinden, David-Alexandre Trégouët, Eco J. C. de Geus, Mohsen Ghanbari, Chunyu Liu, Jennifer A. Brody, Lannie Ligthart, Lei Du, W. David Hill, Vinh Truong, Epidemiology, Internal Medicine, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), University of Toronto, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Department of Epidemiology [Rotterdam], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), VU University medical center, Biological Psychology, APH - Personalized Medicine, APH - Mental Health, APH - Methodology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, and APH - Health Behaviors & Chronic Diseases
- Subjects
0301 basic medicine ,Netherlands Twin Register (NTR) ,medicine.medical_specialty ,Aging ,[SDV]Life Sciences [q-bio] ,Immunology ,030204 cardiovascular system & hematology ,Biology ,Fibrinogen ,Biochemistry ,Hemostatics ,Thrombosis and Hemostasis ,Epigenesis, Genetic ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,SDG 3 - Good Health and Well-being ,Internal medicine ,medicine ,Humans ,Epigenetics ,Gene ,ComputingMilieux_MISCELLANEOUS ,Hemostasis ,medicine.diagnostic_test ,Age Factors ,Cell Biology ,Hematology ,DNA Methylation ,3. Good health ,030104 developmental biology ,Endocrinology ,Clotting time ,chemistry ,Plasminogen activator inhibitor-1 ,DNA methylation ,Erratum ,medicine.drug ,Partial thromboplastin time - Abstract
Many hemostatic factors are associated with age and age-related diseases; however, much remains unknown about the biological mechanisms linking aging and hemostatic factors. DNA methylation is a novel means by which to assess epigenetic aging, which is a measure of age and the aging processes as determined by altered epigenetic states. We used a meta-analysis approach to examine the association between measures of epigenetic aging and hemostatic factors, as well as a clotting time measure. For fibrinogen, we performed European and African ancestry–specific meta-analyses which were then combined via a random effects meta-analysis. For all other measures we could not estimate ancestry-specific effects and used a single fixed effects meta-analysis. We found that 1-year higher extrinsic epigenetic age as compared with chronological age was associated with higher fibrinogen (0.004 g/L/y; 95% confidence interval, 0.001-0.007; P = .01) and plasminogen activator inhibitor 1 (PAI-1; 0.13 U/mL/y; 95% confidence interval, 0.07-0.20; P = 6.6 × 10−5) concentrations, as well as lower activated partial thromboplastin time, a measure of clotting time. We replicated PAI-1 associations using an independent cohort. To further elucidate potential functional mechanisms, we associated epigenetic aging with expression levels of the PAI-1 protein encoding gene (SERPINE1) and the 3 fibrinogen subunit-encoding genes (FGA, FGG, and FGB) in both peripheral blood and aorta intima-media samples. We observed associations between accelerated epigenetic aging and transcription of FGG in both tissues. Collectively, our results indicate that accelerated epigenetic aging is associated with a procoagulation hemostatic profile, and that epigenetic aging may regulate hemostasis in part via gene transcription.
- Published
- 2018
39. The mir-200 family regulates key pathogenic events in ascending aortas of individuals with bicuspid aortic valves
- Author
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Anders Franco-Cereceda, Jesper R. Gådin, Otto Bergman, Flore-Anne Poujade, Shohreh Maleki, Hanna M. Björck, S. Y. Chan, Anirban Bhattachariya, K. A. Cottrill, Nancy Simon, Karin Lundströmer, and Per Eriksson
- Subjects
0301 basic medicine ,Male ,Proteomics ,Epithelial-Mesenchymal Transition ,Heart Valve Diseases ,030204 cardiovascular system & hematology ,03 medical and health sciences ,Aortic aneurysm ,0302 clinical medicine ,Aneurysm ,Bicuspid aortic valve ,Bicuspid Aortic Valve Disease ,medicine.artery ,Ascending aorta ,Gene expression ,microRNA ,Internal Medicine ,medicine ,Humans ,Epithelial–mesenchymal transition ,Transcription factor ,Aorta ,Zinc Finger E-box Binding Homeobox 2 ,business.industry ,Zinc Finger E-box-Binding Homeobox 1 ,medicine.disease ,3. Good health ,Aortic Aneurysm ,MicroRNAs ,030104 developmental biology ,Gene Expression Regulation ,Aortic Valve ,cardiovascular system ,Cancer research ,Female ,business ,Signal Transduction - Abstract
Background An individual with a bicuspid aortic valve (BAV) runs a substantially higher risk of developing aneurysm in the ascending aorta compared to the normal population with tricuspid aortic valves (TAV). Aneurysm formation in patients with BAV and TAV is known to be distinct at the molecular level but the underlying mechanisms are undefined. Here, we investigated the still incompletely described role of microRNAs (miRNAs), important post-transcriptional regulators of gene expression, in such aortic disease of patients with BAV as compared with TAV. Methods and results Using a system biology approach, based on data obtained from proteomic analysis of non-dilated aortas from BAV and TAV patients, we constructed a gene-interaction network of regulatory microRNAs associated with the observed differential protein signature. The miR-200 family was the highest ranked miRNA, hence potentially having the strongest effect on the signalling network associated with BAV. Further, qRT-PCR and ChIP analyses showed lower expression of miR-200c, higher expression of miR-200 target genes, ZEB1/ZEB2 transcription factors, and higher chromatin occupancy of the miR-200c promoter by ZEB1/ZEB2 in BAV patients, indicating a miR-200c/ZEBs negative feedback loop and induction of endothelial/epithelial mesenchymal transition (EndMT/EMT). Conclusion We propose that a miR-200-dependent process of EndMT/EMT is a plausible biological mechanism rendering the BAV ascending aorta more prone to aneurysm development. Although initially supported by a miR-200c/ZEB feedback loop, this process is most probably advanced by cooperation of other miRNAs.
- Published
- 2018
40. Aneurysm Development in Patients With a Bicuspid Aortic Valve Is Not Associated With Transforming Growth Factor-β Activation
- Author
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Jan H.M. Lindeman, Shaukat Khan, Joy Roy, Lei Du, Takeshi Tsuda, Salah A. Mohamed, Hanna M. Björck, Anders Franco-Cereceda, Jesper R. Gådin, Valentina Paloschi, Per Eriksson, and Shohreh Maleki
- Subjects
Adult ,Male ,Aortic valve ,medicine.medical_specialty ,bicuspid aortic valve ,Heart Valve Diseases ,Receptor, Transforming Growth Factor-beta Type I ,Smad Proteins ,Protein Serine-Threonine Kinases ,Aortic aneurysm ,Aneurysm ,Bicuspid aortic valve ,Bicuspid Aortic Valve Disease ,Transforming Growth Factor beta ,Internal medicine ,medicine.artery ,Ascending aorta ,medicine ,Humans ,Phosphorylation ,Cells, Cultured ,Aged ,Aged, 80 and over ,Principal Component Analysis ,Tricuspid valve ,Vascular disease ,business.industry ,Gene Expression Profiling ,Middle Aged ,medicine.disease ,Aortic Aneurysm ,Extracellular Matrix ,medicine.anatomical_structure ,Gene Expression Regulation ,Latent TGF-beta Binding Proteins ,Aortic Valve ,aneurysm ,cardiovascular system ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,Receptors, Transforming Growth Factor beta ,Signal Transduction ,Transforming growth factor - Abstract
Objective— Patients with bicuspid aortic valve (BAV) have an increased risk of developing ascending aortic aneurysms. Transforming growth factor-β (TGFβ) is a crucial factor of vascular remodeling, the impaired signaling of which can alter the structure and composition of the extracellular matrix. In this study, we analyzed the activity of TGFβ in aneurysmal and nonaneurysmal ascending aorta from BAV patients, using tricuspid aortic valve (TAV) patients as a reference group. Approach and Results— The response to exogenous TGFβ was analyzed with regard to gene expression in primary aortic smooth muscle cells that were isolated from 7 BAV and 5 TAV patients and in valve fibroblasts from 7 BAV and 8 TAV patients. The set of genes that were significantly changed by TGFβ (217 genes) was compared with gene expression profiles of the ascending aorta from BAV and TAV patients (139 arrays). By principle component analysis, based on the 217 genes, gene expression differed significantly in the intima/media region between aneurysmal BAV and TAV aortas, driven by the response in TAV patients. During aneurysm development the levels of phosphorylated SMADs and the availability of free TGFβ were lower in BAV patients compared with TAV. Confocal microscopy analysis showed a higher colocalization of latency associated peptide and latent TGFβ binding protein 3 in BAV aortas. Conclusions— Our findings suggest that TGFβ activation during aneurysm formation is muted in patients with BAV, possibly as a result of an increased TGFβ sequestration in the extracellular space.
- Published
- 2015
41. Biomechanical Properties of the Thoracic Aneurysmal Wall: Differences Between Bicuspid Aortic Valve and Tricuspid Aortic Valve Patients
- Author
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Caroline Forsell, T. Christian Gasser, Hanna M. Björck, Anders Franco-Cereceda, and Per Eriksson
- Subjects
Male ,Pulmonary and Respiratory Medicine ,Aortic valve ,medicine.medical_specialty ,Collagen orientation ,Finite Element Analysis ,Heart Valve Diseases ,Bicuspid aortic valve ,Bicuspid Aortic Valve Disease ,Wall stiffness ,Tensile Strength ,Internal medicine ,medicine.artery ,medicine ,Humans ,In patient ,Aged ,Aorta ,Aortic Aneurysm, Thoracic ,business.industry ,Middle Aged ,medicine.disease ,Biomechanical Phenomena ,medicine.anatomical_structure ,Aortic Valve ,cardiovascular system ,Cardiology ,Molecular mechanism ,Female ,Surgery ,Collagen ,Tricuspid Valve ,Cardiology and Cardiovascular Medicine ,Wall thickness ,business - Abstract
Background The prevalence for thoracic aortic aneurysms (TAAs) is significantly increased in patients with a bicuspid aortic valve (BAV) compared with patients who have a normal tricuspid aortic valve (TAV). TAA rupture is a life-threatening event, and biomechanics-based simulations of the aorta may help to disentangle the molecular mechanism behind its development and progression. The present study used polarized microscopy and macroscopic in vitro tensile testing to explore collagen organization and mechanical properties of TAA wall specimens from BAV and TAV patients. Methods Circumferential sections of aneurysmal aortic tissue from BAV and TAV patients were obtained during elective operations. The distribution of collagen orientation was captured by a Bingham distribution, and finite element models were used to estimate constitutive model parameters from experimental load-displacement curves. Results Collagen orientation was almost identical in BAV and TAV patients, with a highest probability of alignment along the circumferential direction. The strength was almost two times higher in BAV samples (0.834 MPa) than in TAV samples (0.443 MPa; p C f ) was significantly increased in BAV compared with TAV patients ( C f = 7.45 MPa vs 3.40 MPa; p = 0.003), whereas the elastin-related stiffness was similar in both groups. A trend toward a decreased wall thickness was seen in BAV patients ( p = 0.058). Conclusions The aneurysmal aortas of BAV patients show a higher macroscopic strength, mainly due to an increased collagen-related stiffness, compared with TAV patients. The increased wall stiffness in BAV patients may contribute to the higher prevalence for TAAs in this group.
- Published
- 2014
42. Long-term Outcome after Thrombolysis for Acute Lower Limb Ischaemia
- Author
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O, Grip, A, Wanhainen, S, Acosta, and M, Björck
- Subjects
Male ,Sweden ,Time Factors ,Databases, Factual ,Embolism ,Graft Occlusion, Vascular ,Thrombosis ,Aneurysm ,Peripheral Arterial Disease ,Treatment Outcome ,Fibrinolytic Agents ,Lower Extremity ,Ischemia ,Humans ,Female ,Thrombolytic Therapy ,Vascular Patency ,Aged ,Retrospective Studies - Abstract
The purpose was to study long-term outcome after thrombolysis for acute arterial lower limb ischaemia, and to evaluate the results depending on the underlying aetiology of arterial occlusion.This was a retrospective study of patients entered into a prospective database. Patients were identified in prospective databases from two vascular centres, including a large number of variables. Case records were analysed retrospectively. Through cross linkage with the Population Registry 100% accurate survival data were obtained. Between January 2001 and December 2013, 689 procedures were included. The aetiology of ischaemia was graft/stent/stent graft occlusion in 39.8%, arterial thrombosis in 27.7%, embolus in 25.1% and popliteal aneurysm in 7.4%.The mean follow-up was 59.4 months (95% CI, 56.1-62.7), during which 32.9% needed further re-interventions, 16.4% underwent amputation without re-intervention, and 50.7% had no re-intervention. The need for re-intervention during follow-up was 48.0% in the graft/stent occlusions group, 34.0% of the popliteal aneurysm group, 25.4% in the thrombosis group, and 16.3% in the embolus group (p .001). The overall primary patency rates were 69.1% and 55.9% at 1 and 5 years, respectively. Primary patency at 5 years was higher for the embolus group (83.3%, p = .002) and lower for the occluded graft/stent group (43.3%, p .001). Secondary patency rates were 80.1% and 75.2% at 1 and 5 years, respectively, without difference between the subgroups. The amputation rate was lower in the embolic group at 1 and 5 years (8.1% and 11.1%, respectively, p = .001). Survival was higher in the group with occluded popliteal aneurysms at 5 years (83.3%, p = 0.004). Amputation free survival was 72.1% and 45.2% at 1 and 5 years; lower in the occluded graft/stent group at five years (37.9%, p = .007).Intra-arterial thrombolytic therapy achieves good medium and long-term clinical outcome, reducing the need of open surgical treatment in most patients.
- Published
- 2016
43. Outcomes of Patients with Critical Limb Ischaemia in the EUCLID Trial
- Author
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L. Norgren, M.R. Patel, W.R. Hiatt, D.M. Wojdyla, F.G.R. Fowkes, I. Baumgartner, K.W. Mahaffey, J.S. Berger, W.S. Jones, B.G. Katona, P. Held, J.I. Blomster, F.W. Rockhold, and M. Björck
- Subjects
Surgery ,Cardiology and Cardiovascular Medicine - Published
- 2018
44. Gender Differences In Patients With Bicuspid Aortic Valves
- Author
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Anders Franco-Cereceda, Christian Olsson, Per Eriksson, Hanna M. Björck, M. Vignac, and Bamba Gaye
- Subjects
medicine.medical_specialty ,business.industry ,Internal medicine ,Cardiology ,Medicine ,In patient ,Cardiology and Cardiovascular Medicine ,business - Published
- 2019
45. Prediction Of The Development Of Aortic Dilatation In Patients With Bicuspid (Bav) Versus Tricuspid (Tav) Aortic Valves
- Author
-
B. Gaye, Christian Olsson, Hanna M. Björck, Anders Franco-Cereceda, M. Vignac, and Per Eriksson
- Subjects
Aortic dilatation ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Cardiology ,In patient ,Cardiology and Cardiovascular Medicine ,business - Published
- 2019
46. Five Year Outcomes in Men Screened for Carotid Artery Stenosis at 65 Years of Age: A Population Based Cohort Study
- Author
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D. Högberg, M. Björck, K. Mani, S. Svensjö, and A. Wanhainen
- Subjects
Surgery ,Cardiology and Cardiovascular Medicine - Published
- 2019
47. Mesenchymal state of intimal cells may explain higher propensity to ascending aortic aneurysm in bicuspid aortic valves
- Author
-
Johan Petrini, Anders Franco-Cereceda, Per Eriksson, Rui M. M. Branca, Valentina Paloschi, Jonas Fuxe, Shohreh Maleki, Lei Du, Joëlle Magné, Kjell Hultenby, Janne Lehtiö, Hanna M. Björck, and Sanela Kjellqvist
- Subjects
0301 basic medicine ,Aortic valve ,medicine.medical_specialty ,Epithelial-Mesenchymal Transition ,Proteome ,Heart Valve Diseases ,Hemodynamics ,030204 cardiovascular system & hematology ,Article ,03 medical and health sciences ,Aortic aneurysm ,0302 clinical medicine ,Bicuspid aortic valve ,Aneurysm ,Bicuspid Aortic Valve Disease ,Internal medicine ,medicine.artery ,Ascending aorta ,medicine ,Humans ,Epithelial–mesenchymal transition ,Mammary Arteries ,Multidisciplinary ,Receptors, Notch ,business.industry ,Mesenchymal Stem Cells ,medicine.disease ,Tunica intima ,Endocytosis ,Aortic Aneurysm ,030104 developmental biology ,medicine.anatomical_structure ,Aortic Valve ,cardiovascular system ,Cardiology ,Tunica Intima ,rhoA GTP-Binding Protein ,business - Abstract
Individuals with a bicuspid aortic valve (BAV) are at significantly higher risk of developing aortic complications than individuals with tricuspid aortic valves (TAV) and defective signaling during the embryonic development and/or life time exposure to abnormal hemodynamic have been proposed as underlying factors. However, an explanation for the molecular mechanisms of aortopathy in BAV has not yet been provided. We combined proteomics, RNA analyses, immunohistochemistry, and electron microscopy to identify molecular differences in samples of non-dilated ascending aortas from BAV (N = 62) and TAV (N = 54) patients. Proteomic analysis was also performed for dilated aortas (N = 6 BAV and N = 5 TAV) to gain further insight into the aortopathy of BAV. Our results collectively showed the molecular signature of an endothelial/epithelial-mesenchymal (EndMT/EMT) transition-like process, associated with instability of intimal cell junctions and activation of RHOA pathway in the intima and media layers of ascending aorta in BAV patients. We propose that an improper regulation of EndMT/EMT during the spatiotemporally related embryogenesis of semilunar valves and ascending aorta in BAV individuals may result in aortic immaturity and instability prior to dilation. Exasperation of EndMT/EMT state in post embryonic life and/or exposure to non-physiological hemodynamic could lead to the aneurysm of ascending aorta in BAV individuals.
- Published
- 2016
48. Abstract 500: DNA Methylation Profiling Reveals an Epithelial/Endothelial-Mesenchymal Transition-like Signature of Intima-Media Cells in the Ascending Aorta of Bicuspid Aortic Valve Patients
- Author
-
Shohreh Maleki, Per Eriksson, Silvia Pulignani, Hanna M. Björck, Anders Franco-Cereceda, Valentina Paloschi, and Lei Du
- Subjects
Pathology ,medicine.medical_specialty ,Aorta ,Methylation ,Biology ,medicine.disease ,Bioinformatics ,Actin filament bundle ,Aortic aneurysm ,Differentially methylated regions ,Bicuspid aortic valve ,medicine.artery ,DNA methylation ,Ascending aorta ,cardiovascular system ,medicine ,Cardiology and Cardiovascular Medicine - Abstract
Introduction: Individuals with bicuspid aortic valves (BAV) are at increased risk of ascending aortic aneurysm than individuals with tricuspid aortic valves (TAV), but the underlying mechanism is not fully understood. Aberrant DNA methylation has been described in various human diseases, and we have shown that key enzymes in the methylation machinery are differentially expressed in the aortic intima-media of BAV and TAV patients. In the present study, we assessed the hypothesis that DNA methylation may play an important role during aneurysm formation in BAV. We undertook a global methylation approach to delineate biological processes associated with BAV aortopathy, using TAV as a reference. Methods: Ascending aortic biopsies were collected from 21 BAV and 24 TAV patients, with either a non-dilated or a dilated aorta, at the time of surgery. Global DNA methylation was measured in the intima-media layer using Illumina 450k Array. Gene expression was analyzed in the same samples using Affymetrix Exon Array. Results: Compared with TAV, the BAV dilated aorta was hypomethylated (P=0.031), correlating with an up-regulation of global gene expression. A total of 4913 differentially methylated regions (DMRs) were identified and Hallmark analysis of the DMR-associated genes with a fold change of 10% (n=3147) showed a gene signature of Epithelial Mesenchymal Transition (EMT) (FDR q=2.91e-29). This was further confirmed by functional annotation analysis of hypomethylated DMRs using the Genomic Regions Enrichment of Annotations Tool (Stanford University), showing association to actin filament bundle (P=7.09e-12), stress fibers (P=1.72e-11) and adherence junctions (P=2.97e-8). Interestingly, analysis of non-dilated BAV and TAV aorta revealed that genes involved in EMT were the most differentially methylated genes prior to dilatation (FDR q=1.18e-6). We further confirmed the EMT-related molecular signature by immunostaining of some key players of EMT. In conclusion, epigenetic profiling clearly revealed differential methylation between BAV and TAV aorta, particularly in EMT-related genes. Aberrant EMT in the ascending aorta prior to dilatation may constitute the basis for the increased aneurysm susceptibility in BAV patients.
- Published
- 2016
49. The association between circulating angiotensin-converting enzyme and cardiovascular risk in the elderly: a cross-sectional study
- Author
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Urban Alehagen, Toste Länne, Liza U. Ljungberg, Karin Persson, Ulf Dahlström, Rachel De Basso, and Hanna M. Björck
- Subjects
Male ,Medicin och hälsovetenskap ,Medicine (General) ,medicine.medical_specialty ,endothelium ,Endothelium ,Cross-sectional study ,Cardiovascular risk factors ,Disease ,Peptidyl-Dipeptidase A ,Medical and Health Sciences ,smoking ,R5-920 ,Endocrinology ,INDEL Mutation ,Risk Factors ,Internal medicine ,Diabetes mellitus ,Genotype ,Internal Medicine ,medicine ,Humans ,genetics ,Genetic Predisposition to Disease ,Aged ,Aged, 80 and over ,Sweden ,Polymorphism, Genetic ,biology ,business.industry ,Angiotensin-converting enzyme ,medicine.disease ,Cross-Sectional Studies ,medicine.anatomical_structure ,dibetes ,Cardiovascular Diseases ,biology.protein ,Population study ,Female ,business - Abstract
INTRODUCTION: A polymorphism in the angiotensin-converting enzyme gene (ACE I/D polymorphism) has been associated with increased risk for cardiovascular disease (CVD). This polymorphism affects the level of circulating ACE, but there is great individual variation, even between those with the same genotype. Few previous studies have investigated the link between circulating ACE and cardiovascular risk. The aim of this study was to investigate this association, and to examine the relationship between ACE level, ACE genotype and CVD. MATERIALS AND METHODS: The study population consisted of 322 men and 350 women aged 69-87. Plasma ACE level was determined using enzyme-linked immunosorbent assay (ELISA), and ACE genotype was analysed using PCR followed by gel electrophoresis. RESULTS: In men, ACE levels increased with increasing number of cardiovascular risk factors (p = 0.003). There was a significant association in men between increased ACE level and both diabetes (p = 0.007) and smoking (p = 0.037). CONCLUSIONS: This study shows that cardiovascular risk factors (such as smoking and diabetes) are associated with higher levels of circulating ACE in men. High ACE levels may represent one of the cellular mechanisms involved in producing the vascular damage associated with cardiovascular risk factors. Funding Agencies|Cardiovascular Inflammatory Research Center, Linkoping, Sweden||Swedish Research Council|1216|Elanora Demeroutis Foundation, Linkoping, Sweden|LIO-28471|Goljes Memorial Foundation, Sweden|LA2009-0119|Medical Research Council of South East Sweden|FORSS-34931
- Published
- 2011
50. P178DNA methylation in bicuspid aortic valve aortopathy: potential contribution of oscillatory flow to an epithelial-to-mesenchymal transition signature
- Author
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Karin Lundströmer, Lei Du, Anders Franco-Cereceda, Per Eriksson, A Evangelista, Aleksandra Kostina, Hanna M. Björck, Valentina Paloschi, Shohreh Maleki, and S Pulignani
- Subjects
Bicuspid aortic valve ,Physiology ,Chemistry ,Physiology (medical) ,medicine ,Methylation ,Epithelial–mesenchymal transition ,Cardiology and Cardiovascular Medicine ,Signature (topology) ,medicine.disease ,Oscillatory flow ,Cell biology - Published
- 2018
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