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HDLs and the pathogenesis of atherosclerosis

Schwertani, Adel; Choi, Hong, Y.; Genest, Jacques

Current Opinion in Cardiology: May 2018 - Volume 33 - Issue 3 - p 311–316
doi: 10.1097/HCO.0000000000000508
MOLECULAR GENETICS: Edited by Ali J. Marian

Purpose of review Plasma levels of HDL cholesterol are a biomarker of cardiovascular health but not a therapeutic target, as demonstrated by the failure of pharmacological modulation of HDL cholesterol to prevent or treat atherosclerotic cardiovascular disease. In health, HDL particles exert pleiotropic effects against atherosclerosis, including cholesterol removal from foam cells, vasodilatory effects through vascular endothelial cell nitric oxide production, decreased vascular inflammation and oxidative damage, endothelial cell proliferation and antiapoptotic effects.

Recent findings These functional effects of HDL are independent of the cholesterol mass and are related to the proteome and lipidome. In disease states and with the ageing process, HDL components are extensively modified and may no longer play a beneficial role but are retained in the atheroma and contribute to atherosclerosis. We have recently shown that desmocollin 1 (DSC1) acts as an apolipoprotein (apo) A-I binding protein that is highly expressed in atherosclerotic plaques and inhibits atheroprotective HDL functions by retaining apoA-I. The apoA-I retention hypothesis proposes that macrophages express DSC1 in a maladaptive process that renders apoA-I inactive and contributes to atherosclerosis.

Summary HDL loses their beneficial properties in ageing and disease states. Novel pathways may present new therapeutic avenues to restore their biological functions.

Division of Cardiology, Research Institute of the McGill University Health Centre, Montreal, Québec, Canada

Correspondence to Jacques Genest, MD, Research Institute of the McGill University Health Centre, 1001 boul. Decarie Bloc E, Office EM12212, Montréal, Québec, Canada H4A 3J1. Tel: +1 514 934 1934x34642; e-mail: Jacques.genest@mcgill.ca

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