Regulation of reverse cholesterol transport and clinical implications.
Plasma levels of high-density lipoprotein (HDL) cholesterol and its major protein, apolipoprotein A-I, are inversely correlated with the incidence of atherosclerotic cardiovascular disease. Low HDL cholesterol and apolipoprotein A-I levels often are found in association with other cardiovascular risk factors, including the metabolic syndrome, insulin resistance, and type 2 diabetes mellitus. However, overexpression of apolipoprotein A-I in animals has been shown to reduce progression and even induce regression of atherosclerosis, indicating that apolipoprotein A-I is directly protective against atherosclerosis. A major mechanism by which apolipoprotein A-I inhibits atherosclerosis may be by promoting cholesterol efflux from macrophages and returning it to the liver for excretion, a process termed reverse cholesterol transport. This article focuses on new developments in the regulation of reverse cholesterol transport and the clinical implications of those developments.
Rader
Daniel J
DJ
Preventive Cardiology/Lipid Research Center, University of Pennsylvania Health System, Philadelphia, Pennsylvania 19104, USA. rader@mail.med.upenn.edu
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics; D001692:Biological Transport / Q000235:genetics* / Q000502:physiology; D018955:CD36 Antigens / Q000235:genetics; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D002352:Carrier Proteins / Q000235:genetics; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000235:genetics / Q000378:metabolism*; D006023:Glycoproteins; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007009:Hypolipoproteinemias / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D008049:Lipase / Q000235:genetics; D008071:Lipoprotein Lipase / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D009525:Niacin / Q000627:therapeutic use; D049294:Phospholipid Transfer Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D012307:Risk Factors; D051122:Scavenger Receptors, Class B
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D018955:CD36 Antigens; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D006023:Glycoproteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D009525:Niacin; C410382:LIPG protein, human; D008049:Lipase; C498741:Lipg protein, mouse; D008071:Lipoprotein Lipase