Statins induce apoA-I gene expression at the transcriptional level in HepG2 cells by inhibition of HMG-CoA reductase. (a) Statins induce apoA-I mRNA in HepG2 cells in a dose-dependent manner. HepG2 cells were treated for 24 hours with the indicated doses of cerivastatin or pitavastatin or appropriate solvent in serum-free medium. RNA levels were quantified as described in Methods and expressed (means ± SD, n = 3/point) relative to the untreated control set at 1. Values without a common superscript are significantly different, P < 0.05. R.A.U., relative arbitrary units. (b) Statins induce apoA-I mRNA in HepG2 cells in a time-dependent manner. HepG2 cells were treated for 3, 6, 12, or 24 hours with 5 μM of cerivastatin, or pitavastatin, or appropriate solvent in serum-free medium. RNA levels were quantified as described in Methods and expressed relative to the untreated controls at each time point set at 1. (c) Mevalonate reverses the induction of apoA-I mRNA by statins. HepG2 cells were treated for 24 hours with cerivastatin (5 μM) and/or mevalonate (Mev.; 3 mM) or appropriate solvent in serum-free medium. (d) Statins regulate apoA-I gene expression in HepG2 cells at the transcriptional level. HepG2 cells were treated for 24 hours with cerivastatin (5 μM) or appropriate solvent in serum-free medium. Actinomycin D (Act. D; 5 μg/ml) was added to the medium 90 minutes before treatment. For all, total RNA (10 μg) was subjected to Northern blot analysis using human apoA-I and 36B4 cDNA probes.