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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Elsevier
2025-06-01
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| 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. |
| format | Article |
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| institution | Kabale University |
| issn | 0022-2275 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
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| series | Journal of Lipid Research |
| 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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