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. 2021 Jul 16;11(7):459.
doi: 10.3390/metabo11070459.

Lipoprotein Proteomics and Aortic Valve Transcriptomics Identify Biological Pathways Linking Lipoprotein(a) Levels to Aortic Stenosis

Raphaëlle Bourgeois  1   2 , Jérôme Bourgault  1   2 , Audrey-Anne Despres  1   2 , Nicolas Perrot  1   2 , Jakie Guertin  1   2 , Arnaud Girard  1   2 , Patricia L Mitchell  1 , Clarisse Gotti  3 , Sylvie Bourassa  3 , Corey A Scipione  4 , Nathalie Gaudreault  1 , Michael B Boffa  5 , Marlys L Koschinsky  5 , Philippe Pibarot  1   2 , Arnaud Droit  3   6 , Sébastien Thériault  1   7 , Patrick Mathieu  1   8 , Yohan Bossé  1   9 , Benoit J Arsenault  1   2
Affiliations

Lipoprotein Proteomics and Aortic Valve Transcriptomics Identify Biological Pathways Linking Lipoprotein(a) Levels to Aortic Stenosis

Raphaëlle Bourgeois et al. Metabolites. .

Abstract

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.

Keywords: aortic valve; calcific aortic valve stenosis; lipoprotein(a); proteomics; transcriptomics.

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Conflict of interest statement

The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Enrichment analysis of proteins found to be associated with Lp(a) regardless of (a) CAVS status and (b) in CAVS only. (c) DisGeNET enrichment analysis of proteins found to be associated with CAVS Lp(a) and (d) interaction analysis between the proteins identified as preferentially associated with the CAVS Lp(a) by STRING-db.
Figure 2
Figure 2
(a) Volcano plot showing the genes identified in calcified valve of patients with high versus low Lp(a) and (b) enrichment analysis of genes found to be the most influenced by Lp(a) concentrations in explanted calcified aortic valves of patients with high versus low Lp(a).
See this image and copyright information in PMC

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