HDL as a target in the treatment of atherosclerotic cardiovascular disease.
Lipid abnormalities are among the key risk factors for cardiovascular disease. Indeed, lipid-modifying drugs - in particular, the statins, which primarily lower plasma levels of low-density lipoprotein (LDL) cholesterol - considerably reduce the risk of cardiovascular events, leading to their widespread use. Nevertheless, it seems that there might be limits to the degree of benefit that can be achieved by lowering LDL-cholesterol levels alone, which has led to increased interest in targeting other lipid-related risk factors for cardiovascular disease, such as low levels of high-density lipoprotein (HDL) cholesterol. In this article, we first consider the mechanisms that underlie the protective effect of HDL cholesterol, and then discuss several strategies that have recently emerged to increase levels of HDL cholesterol to treat cardiovascular disease, including nuclear receptor modulation, inhibition of cholesteryl ester transfer protein and infusion of apolipoprotein/phospholipid complexes.
Linsel-Nitschke
Patrick
P
Division of Molecular Medicine, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10027, USA. pl2031@columbia.edu
Tall
Alan R
AR
D000818:Animals; D016632:Apolipoprotein A-I / Q000008:administration & dosage / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000209:etiology; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000097:blood* / Q000235:genetics / Q000502:physiology; D016503:Drug Delivery Systems; D006023:Glycoproteins / Q000037:antagonists & inhibitors*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists*; D012307:Risk Factors
D016632:Apolipoprotein A-I; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D006023:Glycoproteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D047492:Peroxisome Proliferator-Activated Receptors