Niacin decreases removal of high-density lipoprotein apolipoprotein A-I but not cholesterol ester by Hep G2 cells. Implication for reverse cholesterol transport.
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.
Jin
F Y
FY
Cholesterol Center and Gerontology Section, Department of Veterans Affairs Medical Center, Long Beach, CA 90822, USA.
Kamanna
V S
VS
Kashyap
M L
ML
D016632:Apolipoprotein A-I / Q000378:metabolism*; D001692:Biological Transport; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism*; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D009525:Niacin / Q000494:pharmacology*
D016632:Apolipoprotein A-I; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL; D009525:Niacin; D002784:Cholesterol