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A Comparative Analysis of the Lipoprotein(a) and Low-Density Lipoprotein Proteomic Profiles Combining Mass Spectrometry and Mendelian Randomization.

CJC open

Authors: Raphaëlle Bourgeois, Arnaud Girard, Nicolas Perrot, Jakie Guertin, Patricia L Mitchell, Christian Couture, Clarisse Gotti, Sylvie Bourassa, Paolo Poggio, Elvira Mass, Romain Capoulade, Corey A Scipione, Audrey-Anne Després, Patrick Couture, Arnaud Droit, Philippe Pibarot, Michael B Boffa, Sébastien Thériault, Marlys L Koschinsky, Patrick Mathieu, Benoit J Arsenault

BACKGROUND: Lipoprotein(a) (Lp[a]), which consists of a low-density lipoprotein (LDL) bound to apolipoprotein(a), is one of the strongest genetic risk factors for atherosclerotic cardiovascular diseases. Few studies have performed hypothesis-free direct comparisons of the Lp(a) and the LDL proteomes. Our objectives were to compare the Lp(a) and the LDL proteomic profiles and to evaluate the effect of lifelong exposure to elevated Lp(a) or LDL cholesterol levels on the plasma proteomic profile.

METHODS: We performed a label-free analysis of the Lp(a) and LDL proteomic profiles of healthy volunteers in a discovery (n = 6) and a replication (n = 9) phase. We performed inverse variance weighted Mendelian randomization to document the effect of lifelong exposure to elevated Lp(a) or LDL cholesterol levels on the plasma proteomic profile of participants of the INTERVAL study.

RESULTS: We identified 15 proteins that were more abundant on Lp(a) compared with LDL (, , , , , , , , , , , , , , and ). We found no proteins that were more abundant on LDL compared with Lp(a). After correction for multiple testing, lifelong exposure to elevated LDL cholesterol levels was associated with the variation of 18 plasma proteins whereas Lp(a) did not appear to influence the plasma proteome.

CONCLUSIONS: Results of this study highlight marked differences in the proteome of Lp(a) and LDL as well as in the effect of lifelong exposure to elevated LDL cholesterol or Lp(a) on the plasma proteomic profile.

© 2020 Canadian Cardiovascular Society. Published by Elsevier Inc.

PMID: 34027348

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