Prebeta-1 HDL and coronary heart disease

Abstract

A negative correlation between HDL cholesterol levels and risk of coronary artery disease has long been recognized. Emerging knowledge of the molecular speciation and functional properties of HDL provides an opportunity to study the atheroprotective effects of specific metabolic processes. The discovery of the quantum particle among the molecular species of HDL (prebeta-1 HDL) and its role in cholesterol efflux from the artery wall, offer a means of assessing the efficiency of efflux. This review presents observations on the structure and metabolism of this particle and its emerging role as a predictor of risk for atherosclerotic vascular disease. Prebeta-1 HDL is now recognized as the primary acceptor of cholesterol effluxed by the dominant ATP-binding cassette A1 (ABCA1) transporter in arterial macrophages, a critical step in reverse cholesterol transport. Several studies have revealed an association between high levels of this particle and risk of globally defined coronary artery disease and carotid intima-media thickness. Recently, these findings have been confirmed and extended to include myocardial infarction. High levels of prebeta-1 HDL may serve as an index of functional impairment of cholesterol efflux or esterification, either of which would be expected to impede reverse cholesterol transport. Recent studies underscore the critical role of prebeta-1 HDL in reverse cholesterol transport and its use as a marker of risk for structural coronary disease, myocardial infarction, and cerebral vascular disease.