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(Circulation. 1999;100:576-578.)
© 1999 American Heart Association, Inc.

Editorial

Reverse Cholesterol Transport and Atherosclerosis Regression

David K. Spady, MD

From the Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas.

Correspondence to David K. Spady, MD, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75235-8887.

Key Words: Editorials • cholesterol • atherosclerosis

	Introduction

 
Cholesterol is the major component of atherosclerotic plaque. Cholesterol accumulation within atherosclerotic plaque occurs when cholesterol influx into the arterial wall (from apoB-containing lipoproteins) exceeds cholesterol efflux. Increased influx of cholesterol into the arterial wall is accompanied by an increased influx of monocytes/macrophages,¹ which take up oxidized and aggregated LDL and store the cholesterol as esters. Whereas parenchymal cells maintain cholesterol balance by downregulating de novo cholesterol synthesis and LDL receptor expression, macrophages continue to take up cholesterol from apoB-containing lipoproteins via pathways that are not subject to sterol-mediated feedback control. Current strategies to reduce coronary heart disease (CHD) are aimed primarily at reducing the influx of cholesterol into the arterial wall by lowering plasma LDL cholesterol concentrations. Aggressive lowering of plasma LDL levels reduces mortality from CHD,² but protection is not complete, and in a significant proportion of patients, plasma LDL concentrations cannot be lowered to a level that would be predicted to halt the progression of disease. As a consequence, there is great interest in strategies aimed at enhancing cholesterol efflux from the arterial wall and promoting its transport to the liver for excretion.

Cholesterol that is synthesized in extrahepatic tissues or acquired from lipoproteins is returned to the liver for excretion in a process called reverse cholesterol transport.³ The initial step in reverse cholesterol transport is thought to be efflux of cholesterol from cell membranes to acceptor particles in the interstitial fluid. Two models have been proposed with regard to the movement of cholesterol from plasma membrane . . . [Full Text of this Article]

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