High-density lipoproteins in the prevention of cardiovascular disease: changing the paradigm.
High-density-lipoprotein cholesterol (HDL-C) has been identified in population studies as an independent inverse predictor of cardiovascular events. Although the causal nature of this association has been questioned, HDL and its major protein, apolipoprotein (apo)A1, have been shown to prevent and reverse atherosclerosis in animal models. In addition, HDL and apoA1 have several putatively atheroprotective functions, such as the ability to promote efflux of cholesterol from macrophages in the artery wall, inhibit vascular inflammation, and enhance endothelial function. Therefore, HDL-C and apoA1 have been investigated as therapeutic targets for coronary heart disease. However, recent clinical trials with drugs that raise HDL-C, such as niacin and inhibitors of cholesteryl ester transfer protein, have been disappointing. Here, we review the current state of the science regarding HDL as a therapeutic target.
Division of Translational Medicine and Human Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
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Tuteja
Division of Translational Medicine and Human Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
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Rader
D016632:Apolipoprotein A-I / Q000378:metabolism; D001692:Biological Transport; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors; D008076:Cholesterol, HDL / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000235:genetics / Q000378:metabolism*; D058990:Molecular Targeted Therapy
D016632:Apolipoprotein A-I; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL; D002784:Cholesterol