Secondary Logo

Institutional members access full text with Ovid®

Share this article on:

Pharmacologic elevation of high-density lipoproteins: recent insights on mechanism of action and atherosclerosis protection

Meyers, C Daniela; Kashyap, Moti La,b

Current Opinion in Cardiology: July 2004 - Volume 19 - Issue 4 - p 366-373
doi: 10.1097/01.hco.0000126582.27767.87
HDL cholesterol

Purpose of review Despite the best efforts in reduction of low-density lipoprotein cholesterol, most cardiovascular events are not being prevented. Because high-density lipoprotein (HDL) promotes reverse cholesterol transport and other antiatherogenic effects, interventions aimed at raising HDL cholesterol or mimicking its beneficial effects may greatly improve treatment and prevention of cardiovascular disease. This article reviews the antiatherogenic effects of HDL, recent insights into the mechanisms of action of currently available, and emerging HDL-based therapies.

Recent findings New insights into the basic science of HDL function and metabolism (such as the discovery of β-chain ATP synthase as a hepatic catabolic HDL receptor) are further characterizing the importance of HDL in atheroprotection and identifying novel targets of drug development. Nicotinic acid, fibrates, statins, and thiazolidinediones not only increase HDL cholesterol but also alter HDL subpopulation size and composition. Furthermore, these drugs promote direct antiatherogenic effects of HDL (antioxidation, anti-inflammation, antithrombotic effects, endothelial stabilization). Emerging HDL-raising therapies (such as cholesteryl ester transfer protein inhibitors and 1,2-dimyristoyl-sn-glycero-phosphocholine) and novel interventions that mimic HDL’s beneficial effects (such as apolipoprotein AImilano and apolipoprotein AI mimetic peptides) are proving beneficial in animal and human studies.

Summary An understanding of the atheroprotective mechanisms of HDL is essential for the rational use of currently available drugs and directed development of new drugs. Increasing total HDL cholesterol may not be as important as increasing the functional properties of HDL. Cardiovascular disease treatment and prevention can be improved by combining current low-density lipoprotein-based strategies with effective HDL-based interventions.

aAtherosclerosis Research Center, VA Long Beach Healthcare System, Long Beach, California, USA, bGerontology Section, VA Long Beach Healthcare System, Long Beach, California, USA, and Cardiology Division, University of California, Irvine, Irvine, California, USA

This work was funded by a VA merit review grant and an unrestricted grant from Kos Pharmaceuticals.

Correspondence to Moti L. Kashyap, MD, Veterans Affairs Health Care System, 5901 East 7th Street (11-111I), Long Beach, CA 90822, USA

E-mail: moti.kashyap@med.va.gov

© 2004 Lippincott Williams & Wilkins, Inc.