Pitavastatin, a Potent Hydroxymethylglutaryl Coenzyme a Reductase Inhibitor, Increases Cholesterol 7 α-Hydroxylase Gene Expression in HepG2 Cells

概要

論文の詳細を見る
Background The effect of pitavastatin on the mRNA levels of apolipoprotein (apo) A-I, peroxisome proliferator-activated receptor a (PPARα), cholesterol 7≪-hydroxylase (CYP7A1), and farnesoid X receptor (FXR) in HepG2 cells was examined to establish whether pitavastatin affects bile acid synthesis and if so, to determine a possible molecular mechanism. Methods and Results HepG2 cells were cultured in serum-free Dulbecco's modified Eagle medium for 18 h before drug treatment. Total RNA was extracted at set times and mRNA levels were quantified by reverse transcription-real time polymerase chain reaction. Pitavastatin at 0.1,1, 5, and 10 μmol/L increased the mRNA levels of apo A-I, PPARa, CYP7A1, and FXR in a dose-dependent manner. The mRNA levels of apo A-I, PPARa, CYP7A1, and FXR similarly increased with increasing doses of pitavastatin. Coincubation of mevalonate (4mmol/L) with pitavastatin (5 μmol/L) reversed the inductive effects of pitavastatin on the mRNA levels of these genes, indicating that the inductive effects of pitavastatin were related to its inhibition of HMG-CoA reductase. Conclusions Pitavastatin increased the mRNA levels of CYP7A1 in HepG2 cells, suggesting that increased conversion of cholesterol to bile acids may be the mechanism for its potent low-density lipoprotein cholesterollowering effects.
社団法人日本循環器学会の論文
2004-10-20