{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T14:52:45Z","timestamp":1788965565776,"version":"build-2803163510"},"reference-count":85,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T00:00:00Z","timestamp":1626393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["FRN155226 and FRN149068"],"award-info":[{"award-number":["FRN155226 and FRN149068"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Lipoprotein(a) (Lp(a)) is one of the most important risk factors for the development of calcific aortic valve stenosis (CAVS). However, the mechanisms through which Lp(a) causes CAVS are currently unknown. Our objectives were to characterize the Lp(a) proteome and to identify proteins that may be differentially associated with Lp(a) in patients with versus without CAVS. Our second objective was to identify genes that may be differentially regulated by exposure to high versus low Lp(a) levels in explanted aortic valves from patients with CAVS. We isolated Lp(a) from the blood of 21 patients with CAVS and 22 volunteers and performed untargeted label-free analysis of the Lp(a) proteome. We also investigated the transcriptomic signature of calcified aortic valves from patients who underwent aortic valve replacement with high versus low Lp(a) levels (n = 118). Proteins involved in the protein activation cascade, platelet degranulation, leukocyte migration, and response to wounding may be associated with Lp(a) depending on CAVS status. The transcriptomic analysis identified genes involved in cardiac aging, chondrocyte development, and inflammation as potentially influenced by Lp(a). Our multi-omic analyses identified biological pathways through which Lp(a) may cause CAVS, as well as key molecular events that could be triggered by Lp(a) in CAVS development.<\/jats:p>","DOI":"10.3390\/metabo11070459","type":"journal-article","created":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T10:52:58Z","timestamp":1626432778000},"page":"459","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Lipoprotein Proteomics and Aortic Valve Transcriptomics Identify Biological Pathways Linking Lipoprotein(a) Levels to Aortic Stenosis"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4789-2742","authenticated-orcid":false,"given":"Rapha\u00eblle","family":"Bourgeois","sequence":"first","affiliation":[{"name":"Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec, Qu\u00e9bec, QC G1V 4G5, Canada"},{"name":"Department of Medicine, Faculty of Medicine, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5803-353X","authenticated-orcid":false,"given":"J\u00e9r\u00f4me","family":"Bourgault","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec, Qu\u00e9bec, QC G1V 4G5, Canada"},{"name":"Department of Medicine, Faculty of Medicine, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey-Anne","family":"Despres","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec, Qu\u00e9bec, QC G1V 4G5, Canada"},{"name":"Department of Medicine, Faculty of Medicine, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Perrot","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec, Qu\u00e9bec, QC G1V 4G5, Canada"},{"name":"Department of Medicine, Faculty of Medicine, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6973-5713","authenticated-orcid":false,"given":"Jakie","family":"Guertin","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec, Qu\u00e9bec, QC G1V 4G5, Canada"},{"name":"Department of Medicine, Faculty of Medicine, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Girard","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec, Qu\u00e9bec, QC G1V 4G5, Canada"},{"name":"Department of Medicine, Faculty of Medicine, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia L.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec, Qu\u00e9bec, QC G1V 4G5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarisse","family":"Gotti","sequence":"additional","affiliation":[{"name":"Proteomics Platform of the CHU de Qu\u00e9bec, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Bourassa","sequence":"additional","affiliation":[{"name":"Proteomics Platform of the CHU de Qu\u00e9bec, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corey A.","family":"Scipione","sequence":"additional","affiliation":[{"name":"Toronto General Research Institute, University Health Network, Toronto, ON M5G 2C4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Gaudreault","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec, Qu\u00e9bec, QC G1V 4G5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B.","family":"Boffa","sequence":"additional","affiliation":[{"name":"Robarts Research Institute, London, ON N6A 5B7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlys L.","family":"Koschinsky","sequence":"additional","affiliation":[{"name":"Robarts Research Institute, London, ON N6A 5B7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Pibarot","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec, Qu\u00e9bec, QC G1V 4G5, Canada"},{"name":"Department of Medicine, Faculty of Medicine, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Droit","sequence":"additional","affiliation":[{"name":"Proteomics Platform of the CHU de Qu\u00e9bec, QC G1V 4G2, Canada"},{"name":"Centre de Recherche du CHU de Qu\u00e9bec, Qu\u00e9bec, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1893-8307","authenticated-orcid":false,"given":"S\u00e9bastien","family":"Th\u00e9riault","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec, Qu\u00e9bec, QC G1V 4G5, Canada"},{"name":"Department of Molecular Biology, Medical Biochemistry and Pathology, Faculty of Medicine, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Mathieu","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec, Qu\u00e9bec, QC G1V 4G5, Canada"},{"name":"Department of Surgery, Faculty of Medicine, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohan","family":"Boss\u00e9","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec, Qu\u00e9bec, QC G1V 4G5, Canada"},{"name":"Department of Molecular Medicine, Faculty of Medicine, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2240-8456","authenticated-orcid":false,"given":"Benoit J.","family":"Arsenault","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec, Qu\u00e9bec, QC G1V 4G5, Canada"},{"name":"Department of Medicine, Faculty of Medicine, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/S0140-6736(06)69208-8","article-title":"Burden of valvular heart diseases: A population-based study","volume":"368","author":"Nkomo","year":"2006","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1093\/ejcts\/ezs455","article-title":"Guidelines on the management 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