Conjugated bile acids are elevated in severe calcific aortic valve stenosis

Calcific aortic valve (AV) stenosis (CAVS) is a disease associated with significant morbidity and mortality in the aging population. Recently, bile acids have been shown to play a significant role in many disease processes, and untargeted metabolomic analyses of CAVS patient valves have shown a disr...

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Main Authors: Hannah Zhang, Negar Atefi, Arun Surendran, Jun Han, David R. Goodlett, Davinder S. Jassal, Ashish Shah, Amir Ravandi
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Journal of Lipid Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S0022227525000902
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author Hannah Zhang
Negar Atefi
Arun Surendran
Jun Han
David R. Goodlett
Davinder S. Jassal
Ashish Shah
Amir Ravandi
author_facet Hannah Zhang
Negar Atefi
Arun Surendran
Jun Han
David R. Goodlett
Davinder S. Jassal
Ashish Shah
Amir Ravandi
author_sort Hannah Zhang
collection DOAJ
description Calcific aortic valve (AV) stenosis (CAVS) is a disease associated with significant morbidity and mortality in the aging population. Recently, bile acids have been shown to play a significant role in many disease processes, and untargeted metabolomic analyses of CAVS patient valves have shown a disrupted bile acid pathway. We aimed to understand the changes in human valvular bile acids in relation to CAVS severity. A total of 100 human AVs were collected from patients undergoing AV replacement surgery. Bile acids were quantified by ultrahigh performance liquid chromatography coupled to MS/MS. Patients with mild aortic stenosis (AS) showed a distinct valvular bile acid composition compared with moderate and severe AS groups, with five bile acids being significantly elevated in patients with moderate and severe AS. These included norcholic, nordeoxycholic, glycodeoxycholic, glycocholic, and taurodeoxycholic acid. When classified by calcification score, five species were significantly different between mild and severe AS groups; four bile acids were similar when stratified based on AS severity. Using K-means clustering, we were able to distinguish valve severity by their bile acid composition. Grouping bile acids by conjugation and by primary versus secondary revealed that conjugated primary and secondary bile acids were significantly increased in stenotic valves compared with the mild AS group. Conjugated bile acids are significantly elevated in the valvular tissue of patients with severe calcific AS. These findings suggest a potential link between liver and gut microbiome physiology and bile acid pathways in contributing to the pathophysiology of valvular stenosis.
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spelling doaj-art-bfa7968ac20f47e18a727c90fd10725f2025-08-20T03:30:32ZengElsevierJournal of Lipid Research0022-22752025-06-0166610083010.1016/j.jlr.2025.100830Conjugated bile acids are elevated in severe calcific aortic valve stenosisHannah Zhang0Negar Atefi1Arun Surendran2Jun Han3David R. Goodlett4Davinder S. Jassal5Ashish Shah6Amir Ravandi7Cardiovascular Lipidomics Laboratory, St. Boniface Hospital, Albrechtsen Research Centre, Winnipeg, MB, Canada; Department of Physiology and Pathophysiology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Mass Spectrometry & Proteomics Core Facility, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, IndiaCardiovascular Lipidomics Laboratory, St. Boniface Hospital, Albrechtsen Research Centre, Winnipeg, MB, Canada; Genome British Columbia Proteomics Centre, University of Victoria, Victoria, BC, CanadaCardiovascular Lipidomics Laboratory, St. Boniface Hospital, Albrechtsen Research Centre, Winnipeg, MB, Canada; Department of Physiology and Pathophysiology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Mass Spectrometry & Proteomics Core Facility, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, IndiaGenome British Columbia Proteomics Centre, University of Victoria, Victoria, BC, Canada; Division of Medical Sciences, University of Victoria, Victoria, BC, CanadaGenome British Columbia Proteomics Centre, University of Victoria, Victoria, BC, Canada; Department of Biology and Microbiology, University of Victoria, Victoria, BC, CanadaDepartment of Physiology and Pathophysiology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Section of Cardiology, Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, CanadaDepartment of Physiology and Pathophysiology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Section of Cardiology, Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Precision Cardiovascular Medicine Group, St. Boniface Hospital Research, Winnipeg, MB, CanadaCardiovascular Lipidomics Laboratory, St. Boniface Hospital, Albrechtsen Research Centre, Winnipeg, MB, Canada; Department of Physiology and Pathophysiology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Section of Cardiology, Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Precision Cardiovascular Medicine Group, St. Boniface Hospital Research, Winnipeg, MB, Canada; For correspondence: Amir RavandiCalcific aortic valve (AV) stenosis (CAVS) is a disease associated with significant morbidity and mortality in the aging population. Recently, bile acids have been shown to play a significant role in many disease processes, and untargeted metabolomic analyses of CAVS patient valves have shown a disrupted bile acid pathway. We aimed to understand the changes in human valvular bile acids in relation to CAVS severity. A total of 100 human AVs were collected from patients undergoing AV replacement surgery. Bile acids were quantified by ultrahigh performance liquid chromatography coupled to MS/MS. Patients with mild aortic stenosis (AS) showed a distinct valvular bile acid composition compared with moderate and severe AS groups, with five bile acids being significantly elevated in patients with moderate and severe AS. These included norcholic, nordeoxycholic, glycodeoxycholic, glycocholic, and taurodeoxycholic acid. When classified by calcification score, five species were significantly different between mild and severe AS groups; four bile acids were similar when stratified based on AS severity. Using K-means clustering, we were able to distinguish valve severity by their bile acid composition. Grouping bile acids by conjugation and by primary versus secondary revealed that conjugated primary and secondary bile acids were significantly increased in stenotic valves compared with the mild AS group. Conjugated bile acids are significantly elevated in the valvular tissue of patients with severe calcific AS. These findings suggest a potential link between liver and gut microbiome physiology and bile acid pathways in contributing to the pathophysiology of valvular stenosis.http://www.sciencedirect.com/science/article/pii/S0022227525000902aortic valve calcificationbile acidscalcific aortic valve stenosisconjugated bile acids
spellingShingle Hannah Zhang
Negar Atefi
Arun Surendran
Jun Han
David R. Goodlett
Davinder S. Jassal
Ashish Shah
Amir Ravandi
Conjugated bile acids are elevated in severe calcific aortic valve stenosis
Journal of Lipid Research
aortic valve calcification
bile acids
calcific aortic valve stenosis
conjugated bile acids
title Conjugated bile acids are elevated in severe calcific aortic valve stenosis
title_full Conjugated bile acids are elevated in severe calcific aortic valve stenosis
title_fullStr Conjugated bile acids are elevated in severe calcific aortic valve stenosis
title_full_unstemmed Conjugated bile acids are elevated in severe calcific aortic valve stenosis
title_short Conjugated bile acids are elevated in severe calcific aortic valve stenosis
title_sort conjugated bile acids are elevated in severe calcific aortic valve stenosis
topic aortic valve calcification
bile acids
calcific aortic valve stenosis
conjugated bile acids
url http://www.sciencedirect.com/science/article/pii/S0022227525000902
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