High-Density Lipoprotein: Is the Good Cholesterol Turning Bad?
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High-Density Lipoprotein: Is the Good Cholesterol Turning Bad? Aysha Inankur & Stephen J. Nicholls & Anisa Jahangiri
Published online: 18 November 2010 # Springer Science+Business Media, LLC 2010
Abstract Low high-density lipoprotein cholesterol (HDL-C) is the most prevalent lipid abnormality in patients with known coronary heart disease (CHD). Since the 1960 s, epidemiologic studies have shown an inverse relationship between HDL-C levels and risk of developing CHD. This data correlates a 1-mg/dL increase in HDL-C with a 2% to 3% reduction in CHD events. The prevalence of low HDL-C among patients with CHD has prompted multiple trials to increase the concentration or mimic the function of HDL in an attempt to reduce cardiovascular events. This review outlines the cardioprotective functions of HDL-C, describes conditions that modify HDL structure and function, and presents an overview of clinical trials on HDL-raising therapies.
A. Inankur Department of Internal Medicine, Division of Endocrinology, Lexington, KY 40536, USA A. Jahangiri Graduate Center for Nutritional Sciences, Lexington, KY 40536, USA A. Jahangiri Cardiovascular Research Center, Lexington, KY 40536, USA A. Jahangiri (*) Department of Internal Medicine, Division of Endocrinology, University of Kentucky Lexington, Rm 533 CT Wethington Bldg 900 S. Limestone Street, Lexington, KY 40536, USA e-mail: [email protected] S. J. Nicholls Departments of Cardiovascular Medicine and Cell Biology, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
Keywords HDL . CETP . apoA-I . Cholesterol efflux . ABCA1 . Statins . PON . SRBI . Niacin . VA-HIT . HATS . ARBITER-2 . ARBITER 6-HALTS . Anacetrapib . Dalcetrapib . SAA . Atherosclerosis . Inflammation . Antioxidant
Introduction Epidemiologic studies have clearly demonstrated that irrespective of plasma low-density lipoprotein (LDL) levels, low plasma concentrations of high-density lipoprotein cholesterol (HDL-C) are a risk factor for coronary artery disease. Indeed, for every 1-mg/dl increase of HDL-C, the risk decreases by 2% to 3% in men and women, respectively [1]. HDL has been termed the “good” cholesterol due to a number of antiatherogenic properties, including its anti-thrombotic and antiapoptotic effects, and its regulation of endothelial function and promotion of insulin secretion and glucose oxidation. However, the major determinants of its atheroprotective potential are its involvement in cholesterol efflux, inflammation, and oxidation. HDL extracts excess cholesterol from peripheral tissues, and by a process termed reverse cholesterol transport (RCT) delivers it to the liver for excretion from the body [2]. HDL contains numerous proteins that may contribute to its protective functions, including apolipoprotein A-I (apoA-I) and the antioxidant enzyme paraoxonase (PON). However, in both chronic and acute inflammatory conditions these components may themselves undergo oxidation and impart an inflammatory phenotype to HDL. In response to the accumulating epidemiologic evidence for an associat
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