Lipoprotein Proteomics and Aortic Valve Transcriptomics Identify Biological Pathways Linking Lipoprotein(a) Levels to Aortic Stenosis
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 di...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-07-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/11/7/459 |
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| author | Raphaëlle Bourgeois Jérôme Bourgault Audrey-Anne Despres Nicolas Perrot Jakie Guertin Arnaud Girard Patricia L. Mitchell Clarisse Gotti Sylvie Bourassa Corey A. Scipione Nathalie Gaudreault Michael B. Boffa Marlys L. Koschinsky Philippe Pibarot Arnaud Droit Sébastien Thériault Patrick Mathieu Yohan Bossé Benoit J. Arsenault |
| author_facet | Raphaëlle Bourgeois Jérôme Bourgault Audrey-Anne Despres Nicolas Perrot Jakie Guertin Arnaud Girard Patricia L. Mitchell Clarisse Gotti Sylvie Bourassa Corey A. Scipione Nathalie Gaudreault Michael B. Boffa Marlys L. Koschinsky Philippe Pibarot Arnaud Droit Sébastien Thériault Patrick Mathieu Yohan Bossé Benoit J. Arsenault |
| author_sort | Raphaëlle Bourgeois |
| collection | DOAJ |
| description | 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 (<i>n</i> = 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. |
| first_indexed | 2024-03-10T09:32:29Z |
| format | Article |
| id | doaj.art-7f696038a0694f9b9265590454a9283a |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-10T09:32:29Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-7f696038a0694f9b9265590454a9283a2023-11-22T04:23:04ZengMDPI AGMetabolites2218-19892021-07-0111745910.3390/metabo11070459Lipoprotein Proteomics and Aortic Valve Transcriptomics Identify Biological Pathways Linking Lipoprotein(a) Levels to Aortic StenosisRaphaëlle Bourgeois0Jérôme Bourgault1Audrey-Anne Despres2Nicolas Perrot3Jakie Guertin4Arnaud Girard5Patricia L. Mitchell6Clarisse Gotti7Sylvie Bourassa8Corey A. Scipione9Nathalie Gaudreault10Michael B. Boffa11Marlys L. Koschinsky12Philippe Pibarot13Arnaud Droit14Sébastien Thériault15Patrick Mathieu16Yohan Bossé17Benoit J. Arsenault18Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC G1V 4G5, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC G1V 4G5, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC G1V 4G5, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC G1V 4G5, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC G1V 4G5, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC G1V 4G5, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC G1V 4G5, CanadaProteomics Platform of the CHU de Québec, QC G1V 4G2, CanadaProteomics Platform of the CHU de Québec, QC G1V 4G2, CanadaToronto General Research Institute, University Health Network, Toronto, ON M5G 2C4, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC G1V 4G5, CanadaRobarts Research Institute, London, ON N6A 5B7, CanadaRobarts Research Institute, London, ON N6A 5B7, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC G1V 4G5, CanadaProteomics Platform of the CHU de Québec, QC G1V 4G2, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC G1V 4G5, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC G1V 4G5, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC G1V 4G5, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC G1V 4G5, CanadaLipoprotein(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 (<i>n</i> = 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.https://www.mdpi.com/2218-1989/11/7/459lipoprotein(a)calcific aortic valve stenosisaortic valveproteomicstranscriptomics |
| spellingShingle | Raphaëlle Bourgeois Jérôme Bourgault Audrey-Anne Despres Nicolas Perrot Jakie Guertin Arnaud Girard Patricia L. Mitchell Clarisse Gotti Sylvie Bourassa Corey A. Scipione Nathalie Gaudreault Michael B. Boffa Marlys L. Koschinsky Philippe Pibarot Arnaud Droit Sébastien Thériault Patrick Mathieu Yohan Bossé Benoit J. Arsenault Lipoprotein Proteomics and Aortic Valve Transcriptomics Identify Biological Pathways Linking Lipoprotein(a) Levels to Aortic Stenosis Metabolites lipoprotein(a) calcific aortic valve stenosis aortic valve proteomics transcriptomics |
| title | Lipoprotein Proteomics and Aortic Valve Transcriptomics Identify Biological Pathways Linking Lipoprotein(a) Levels to Aortic Stenosis |
| title_full | Lipoprotein Proteomics and Aortic Valve Transcriptomics Identify Biological Pathways Linking Lipoprotein(a) Levels to Aortic Stenosis |
| title_fullStr | Lipoprotein Proteomics and Aortic Valve Transcriptomics Identify Biological Pathways Linking Lipoprotein(a) Levels to Aortic Stenosis |
| title_full_unstemmed | Lipoprotein Proteomics and Aortic Valve Transcriptomics Identify Biological Pathways Linking Lipoprotein(a) Levels to Aortic Stenosis |
| title_short | Lipoprotein Proteomics and Aortic Valve Transcriptomics Identify Biological Pathways Linking Lipoprotein(a) Levels to Aortic Stenosis |
| title_sort | lipoprotein proteomics and aortic valve transcriptomics identify biological pathways linking lipoprotein a levels to aortic stenosis |
| topic | lipoprotein(a) calcific aortic valve stenosis aortic valve proteomics transcriptomics |
| url | https://www.mdpi.com/2218-1989/11/7/459 |
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