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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:2020-2028.)
© 1997 American Heart Association, Inc.

Articles

Niacin Decreases Removal of High-Density Lipoprotein Apolipoprotein A-I But Not Cholesterol Ester by Hep G2 Cells

Implication for Reverse Cholesterol Transport

Fu-You Jin; Vaijinath S. Kamanna; ; Moti L. Kashyap

From the Cholesterol Center and Gerontology Section, Medical Service, Department of Veterans Affairs Medical Center, Long Beach and University of California, Irvine.

Correspondence to Moti L. Kashyap, MD, Director, Cholesterol Center, Department of Veterans Affairs Medical Center, 5901 E Seventh St (111GE), Long Beach, CA 90822.

Abstract Niacin (nicotinic acid) is the most potent clinically used agent for increasing plasma HDL and apolipoprotein (apo) A-I. The mechanism by which niacin increases apoA-I is not clearly understood. We have examined the effect of niacin on the hepatic production and removal of apoA-I using Hep G2 cells as an in vitro model. Incubation of Hep G2 cells with niacin resulted in increased accumulation of apoA-I in the medium in a dose-dependent manner. Incorporation of [³H]leucine and [³⁵S]methionine into apoA-I and apoA-I mRNA expression was unchanged by niacin, suggesting that it did not affect apoA-I de novo synthesis. Uptake of radiolabeled HDL protein and HDL apoA-I by Hep G2 cells was significantly reduced to as much as 82.9±2.2% (P=.04) and 84.2±2.8% (P=.02), respectively, of the baseline with increasing concentrations of niacin (0 to 3.0 mmol/L). Specific ¹²⁵I-HDL protein uptake measured with a 50-fold excess of unlabeled HDL was reduced to as much as 78.3±4.8% (P=.005) in niacin-treated cells. The uptake of labeled cholesterol esters in HDL was unaffected by niacin. Niacin also effected a similar decrease in HDL protein uptake, but not cholesterol esters, from apoA-I–containing HDL particles isolated by immunoaffinity. The conditioned medium obtained from Hep G2 cells incubated with niacin significantly (P=.002) increased cholesterol efflux from cultured human fibroblasts. These data indicate a novel mechanism whereby niacin selectively decreases hepatic removal of HDL apoA-I but not cholesterol esters, thereby increasing the capacity of retained apoA-I to augment reverse cholesterol transport.

Key Words: atherosclerosis • coronary artery disease • hepatic HDL uptake • metabolism

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