👤 Soumaya Ben-Aicha

Epidemiologic evidence supported an inverse association between HDL (high-density lipoprotein) cholesterol (HDL-C) levels and atherosclerotic cardiovascular disease (ASCVD), identifying HDL-C as a major cardiovascular risk factor and postulating diverse HDL vascular- and cardioprotective functions beyond their ability to drive reverse cholesterol transport. However, the failure of several clinical trials aimed at increasing HDL-C in patients with overt cardiovascular disease brought into question whether increasing the cholesterol cargo of HDL was an effective strategy to enhance their protective properties. In parallel, substantial evidence supports that HDLs are complex and heterogeneous particles whose composition is essential for maintaining their protective functions, subsequently strengthening the "HDL quality over quantity" hypothesis. The following state-of-the-art review covers the latest understanding as per the roles of HDL in ASCVD, delves into recent advances in understanding the complexity of HDL particle composition, including proteins, lipids and other HDL-transported components and discusses on the clinical outcomes after the administration of HDL-C raising drugs with particular attention to CETP (cholesteryl ester transfer protein) inhibitors. Show less

HDL (high-density lipoprotein) role in atherosclerosis is controversial. Clinical trials with CETP (cholesterylester transfer protein)-inhibitors have not provided benefit. We have shown that HDL remodeling in hypercholesterolemia reduces HDL cardioprotective potential. We aimed to assess whether hypercholesterolemia affects HDL-induced atherosclerotic plaque regression. Approach and Results: Atherosclerosis was induced in New Zealand White rabbits for 3-months by combining a high-fat-diet and double-balloon aortic denudation. Then, animals underwent magnetic resonance imaging (basal plaque) and randomized to receive 4 IV infusions (1 infusion/wk) of HDL isolated from normocholesterolemic (NC-HDL; 75 mg/kg; n=10), hypercholesterolemic (HC-HDL; 75 mg/Kg; n=10), or vehicle (n=10) rabbits. Then, animals underwent a second magnetic resonance imaging (end plaque). Blood, aorta, and liver samples were obtained for analyses. Follow-up magnetic resonance imaging revealed that NC-HDL administration regressed atherosclerotic lesions by 4.3%, whereas, conversely, the administration of HC-HDLs induced a further 6.5% progression ( HDL particles isolated from a hypercholesterolemic milieu lose their ability to regress and stabilize atherosclerotic lesions. Our data suggest that HDL remodeling in patients with co-morbidities may lead to the loss of HDL atheroprotective functions. Show less