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Abstract

Low concentrations of high-density lipoprotein cholesterol (HDL-C) have been associated with increased risk of atherosclerosis in clinical trials, and pathological, genetic, and epidemiological studies. High-density lipoproteins (HDL) have numerous anti-atherogenic properties; however, the process of removing excess cholesterol from lipid-laden macrophages (Reverse Cholesterol Transport (RCT)) is believed to be the predominant mechanism of cardioprotection. Cholesterol efflux, the first step in RCT, is presumed to be the rate-limiting step and has been extensively studied. Cholesterol efflux is influenced by both the quality and quantity of HDL. Physicians use the clinical measure of HDL-C in assessing patient risk of coronary artery disease. Numerous pharmacological agents can alter HDL-C; however, the effect of these changes on cholesterol efflux has been poorly studied. The present study attempts to measure the functional properties (defined herein as "quality") of HDL in patients with pharmacologically-induced changes in HDL-C, in terms of each particle's ability to promote cholesterol efflux from cells. Most studies have measured cholesterol efflux potential at only a single serum concentration, which fails to differentiate between potential differences in quantity and quality. We use serum dose-response curves to measure cholesterol efflux potential from Fu5AH cells and define the affinity constant, apparent Km, as being a good measure of quality. Twenty-three healthy control subjects were recruited to develop normal ranges for the parameter apparent Km. Finally, forty-three experimental subjects were assigned to one of four experimental groups: high pharmacologically-induced HDL-C (>1.55 mmol/L), high non-pharmacologically-induced HDL-C, low pharmacologically-induced HDL-C (1.04 mmol/L, regardless of pharmacological intervention. However, patients with pharmacologically-induced changes in HDL-C when HDL-C