NIACIN DECREASES REMOVAL OF HIGH-DENSITY-LIPOPROTEIN APOLIPOPROTEIN-A-I BUT NOT CHOLESTEROL ESTER BY HEP G2 CELLS - IMPLICATION FOR REVERSECHOLESTEROL TRANSPORT

Niacin (nicotinic acid) is the most potent clinically used agent for i ncreasing plasma HDL and apolipoprotein (apo) A-I. The mechanism by wh ich niacin increases apoA-I is not clearly understood. We have examine d 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 w ith niacin resulted in increased accumulation of apoA-I in the medium in a dose-dependent manner. Incorporation of [H-3]leucine and [S-35]me thionine into apoA-I and apoA-I mRNA expression was unchanged by niaci n, 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 signifi cantly reduced to as much as 82.9+/-2.2% (P=.04) and 84.2+/-2.8% (P=.0 2), respectively, of the baseline with increasing concentrations of ni acin (0 to 3.0 mmol/L). Specific I-125-HDL protein uptake measured wit h 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 cholestero l esters in HDL was unaffected by niacin. Niacin also effected a simil ar decrease in HDL protein uptake, but not cholesterol esters, from ap oA-I-containing HDL particles isolated by immunoaffinity. The conditio ned medium obtained from Hep G2 cells incubated with niacin significan tly (P=.002) increased cholesterol efflux from cultured human fibrobla sts. These data indicate a novel mechanism whereby niacin selectively decreases hepatic removal of HDL apoA-I but not cholesterol esters, th ereby increasing the capacity of retained apoA-I to augment reverse ch olesterol transport.