title: HDL and cardiovascular disease: atherogenic and atheroprotective mechanisms.
abstract: The lipoprotein HDL has two important roles: first, it promotes reverse cholesterol transport, and second, it modulates inflammation. Epidemiological studies show that HDL-cholesterol levels are inversely correlated with the risk of cardiovascular events. However, many patients who experience a clinical event have normal, or even high, levels of HDL cholesterol. Measuring HDL-cholesterol levels provides information about the size of the HDL pool, but does not predict HDL composition or function. The main component of HDL, apolipoprotein A-I (apo A-I), is largely responsible for reverse cholesterol transport through the macrophage ATP-binding cassette transporter ABCA1. Apo A-I can be damaged by oxidative mechanisms, which render the protein less able to promote cholesterol efflux. HDL also contains a number of other proteins that are affected by the oxidative environment of the acute-phase response. Modification of the protein components of HDL can convert it from an anti-inflammatory to a proinflammatory particle. Small peptides that mimic some of the properties of apo A-I have been shown in preclinical models to improve HDL function and reduce atherosclerosis without altering HDL-cholesterol levels. Robust assays to evaluate the function of HDL are needed to supplement the measurement of HDL-cholesterol levels in the clinic.
authors.affiliation: Department of Medicine, David Geffen School of Medicine, UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095-1679, USA. mnavab@mednet.ucla.edu
authors.forename: Mohamad
authors.initials: M
authors.lastname: Navab
authors.forename: Srinivasa T
authors.initials: ST
authors.lastname: Reddy
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Van Lenten
authors.forename: Alan M
authors.initials: AM
authors.lastname: Fogelman
mesh_terms: D016632:Apolipoprotein A-I / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000473:pathology*; D008076:Cholesterol, HDL / Q000378:metabolism* / Q000502:physiology; D008078:Cholesterol, LDL / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000473:pathology; D018384:Oxidative Stress; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL