title: Niacin and cholesterol: role in cardiovascular disease (review).
abstract: Niacin has been widely used as a pharmacologic agent to regulate abnormalities in plasma lipid and lipoprotein metabolism and in the treatment of atherosclerotic cardiovascular disease. Although the use of niacin in the treatment of dyslipidemia has been reported as early as 1955, only recent studies have yielded an understanding about the cellular and molecular mechanism of action of niacin on lipid and lipoprotein metabolism. In brief, the beneficial effect of niacin to reduce triglycerides and apolipoprotein-B containing lipoproteins (e.g., VLDL and LDL) are mainly through: a) decreasing fatty acid mobilization from adipose tissue triglyceride stores, and b) inhibiting hepatocyte diacylglycerol acyltransferase and triglyceride synthesis leading to increased intracellular apo B degradation and subsequent decreased secretion of VLDL and LDL particles. The mechanism of action of niacin to raise HDL is by decreasing the fractional catabolic rate of HDL-apo AI without affecting the synthetic rates. Additionally, niacin selectively increases the plasma levels of Lp-AI (HDL subfraction without apo AII), a cardioprotective subfraction of HDL in patients with low HDL. Using human hepatocytes (Hep G2 cells) as an in vitro model system, recent studies indicate that niacin selectively inhibits the uptake/removal of HDL-apo AI (but not HDL-cholesterol ester) by hepatocytes, thereby increasing the capacity of retained HDL-apo AI to augment cholesterol efflux through reverse cholesterol transport pathway. The studies discussed in this review provide evidence to extend the role of niacin as a lipid-lowering drug beyond its role as a vitamin.
authors.affiliation: Atherosclerosis Research Center, Department of Veterans Affairs Healthcare System, Long Beach, California, USA.
authors.forename: Shobha H
authors.initials: SH
authors.lastname: Ganji
authors.forename: Vaijinath S
authors.initials: VS
authors.lastname: Kamanna
authors.forename: Moti L
authors.initials: ML
authors.lastname: Kashyap
mesh_terms: D000217:Acyltransferases / Q000037:antagonists & inhibitors; D000273:Adipose Tissue / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000378:metabolism; D001055:Apolipoproteins B / Q000097:blood / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000517:prevention & control; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood / Q000378:metabolism; D003327:Coronary Disease / Q000517:prevention & control; D051048:Diacylglycerol O-Acyltransferase; D004791:Enzyme Inhibitors; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D009525:Niacin / Q000008:administration & dosage / Q000502:physiology*; D014280:Triglycerides / Q000096:biosynthesis / Q000097:blood
chemical_list: D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004791:Enzyme Inhibitors; D014280:Triglycerides; D009525:Niacin; D002784:Cholesterol; D000217:Acyltransferases; D051048:Diacylglycerol O-Acyltransferase