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Canadian Journal of Cardiology

High-Density Lipoproteins: Biology, Epidemiology, and Clinical Management

Published:October 20, 2016DOI:https://doi.org/10.1016/j.cjca.2016.09.012

      Abstract

      High-density lipoproteins (HDLs) have multiple pleiotropic effects against arteriosclerosis. Most are independent of the cholesterol mass within HDL particles. Yet, HDL cholesterol (HDL-C) remains a biomarker to assess cardiovascular risk. Whereas the epidemiological association between HDL-C and cardiovascular risk is strong, graded and coherent across populations, Mendelian randomization studies cast doubt on whether HDL-C is causally related to atherosclerotic cardiovascular disease. The apparent failure of HDL-C-raising therapies (fibrates, niacin, and cholesteryl ester transfer protein inhibitors) raises questions about the HDL-C hypothesis. HDL particles are heterogeneous in lipid and protein composition, and thus in size and function. Multiple factors related to oxidation and inflammation might render HDL particles malfunctional or proatherogenic. HDL functionality might be a preferred biomarker and therapeutic target. However, most of the beneficial events of HDL particles occur in the subendothelial layer of arteries and not in plasma. In this report, we review the complexity and controversies surrounding HDL and atherosclerotic cardiovascular disease. Importantly, intimal HDL biogenesis, function, and egress from the arterial wall might hold the key to unlocking the therapeutic potential of HDL.

      Résumé

      Les lipoprotéines de haute densité (HDL) ont de multiples effets pléiotropiques contre l’artériosclérose. La plupart sont indépendants de la masse de cholestérol des particules HDL. Toutefois, le cholestérol HDL demeure un biomarqueur pour évaluer les risques cardiovasculaires. Alors qu’il existe un lien épidémiologique fort, marqué et cohérent entre le cholestérol HDL et les risques cardiovasculaires dans l’ensemble des populations, les études à répartition aléatoire mendélienne remettent en question le lien causal entre le cholestérol HDL et la maladie cardiovasculaire athérosclérotique. L’échec apparent des traitements qui augmentent le cholestérol HDL (fibrates, niacine et inhibiteurs de la protéine de transfert des esters de cholestérol) soulève des questions sur l’hypothèse du cholestérol HDL. Les particules HDL sont hétérogènes quant à leur composition lipidique et protéique et par conséquent, quant à leur taille et leur fonctionnement. De multiples facteurs liés à l’oxydation et à l’inflammation pourraient entraîner un dysfonctionnement des particules HDL ou les rendre pro-athérogènes. La fonctionnalité des HDL pourrait constituer un biomarqueur et une cible thérapeutique privilégiés. Toutefois, la plupart des manifestations bénéfiques des particules HDL se produisent dans la couche sous-endothéliale des artères, et non dans le plasma. Dans le présent article, nous passons en revue la complexité et les controverses qui entourent les HDL et la maladie cardiovasculaire athérosclérotique. Notamment, la biogenèse intimale des HDL, leur fonctionnement et leur évacuation de la paroi artérielle pourraient se révéler la clé de l’exploitation du potentiel thérapeutique des HDL.
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