This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dansky, H. M. Articles by Fisher, E. A. Search for Related Content PubMed PubMed Citation Articles by Dansky, H. M. Articles by Fisher, E. A. Related Collections Lipids Cardiovascular Pharmacology Primary prevention Secondary prevention

(Circulation. 1999;100:1762-1763.)
© 1999 American Heart Association, Inc.

Editorials

High-Density Lipoprotein and Plaque Regression

The Good Cholesterol Gets Even Better

Hayes M. Dansky, MD; Edward A. Fisher, MD, PhD

From the Laboratory of Biochemical Genetics and Metabolism (H.M.D.), The Rockefeller University, New York, NY, and Cardiovascular Institute (E.A.F.), Mount Sinai School of Medicine, New York, NY.

Correspondence to Edward A. Fisher, MD, PhD, Cardiovascular Institute, Mount Sinai School of Medicine, Box 1030, 1 Gustave Levy Place, New York, NY 10029. E-mail edmd-phd.fisher@mssm.edu

Key Words: Editorials • cholesterol • lipoproteins • atherosclerosis

	Introduction

 
Primary and secondary prevention of coronary heart disease (CHD) has focused on lowering the LDL fraction of blood lipids not only because of the strong epidemiological evidence linking LDL to CHD, but also because pharmacological interventions have made it a highly modifiable risk factor. In contrast, although there is compelling epidemiological evidence that a low plasma level of HDL is also a powerful independent risk factor, it has received comparatively less attention as a therapeutic target. Contributing factors for this relative neglect undoubtedly include our poor understanding of the mechanisms by which low HDL increases cardiovascular risk and the fact that the most commonly used lipid-lowering drugs produce small increases in HDL levels.

A variety of clinical and epidemiological studies have shown that apolipoprotein A-I (apoA-I), the major protein present on the surface of HDL particles, correlates with HDL cholesterol (HDL-C) levels, and like HDL, apoA-I correlates inversely with atherosclerosis susceptibility. Historically, experimental studies designed to directly investigate the antiatherogenic properties of apoA-I and HDL particles have been limited to in vitro models, given the limited ability to perform invasive studies in humans. The availability of transgenic and knockout mice and other animals has provided intact models of lipoprotein metabolism and atherosclerosis. Studies of such models have provided direct proof in mammals that an elevated plasma level of apoA-I results in increased HDL and in the inhibition of atherosclerotic lesion formation. For example, 2 independent studies^{1 2} demonstrated that transgenic expression of human apoA-I in hyperlipidemic apoE knockout mice resulted in . . . [Full Text of this Article]

This article has been cited by other articles:

				L. M. Belalcazar, A. Merched, B. Carr, K. Oka, K.-H. Chen, L. Pastore, A. Beaudet, and L. Chan Long-Term Stable Expression of Human Apolipoprotein A-I Mediated by Helper-Dependent Adenovirus Gene Transfer Inhibits Atherosclerosis Progression and Remodels Atherosclerotic Plaques in a Mouse Model of Familial Hypercholesterolemia Circulation, June 3, 2003; 107(21): 2726 - 2732. [Abstract] [Full Text] [PDF]

				R. K. Tangirala, D. Pratico, G. A. FitzGerald, S. Chun, K. Tsukamoto, C. Maugeais, D. C. Usher, E. Pure, and D. J. Rader Reduction of Isoprostanes and Regression of Advanced Atherosclerosis by Apolipoprotein E J. Biol. Chem., January 5, 2001; 276(1): 261 - 266. [Abstract] [Full Text] [PDF]