Mechanisms Of Atorvastatin Affecting Triglyceride And Apolipoprotein A5 In HepG2 Cells

BackgroundElevated plasma triglyceride (TG) is an independent risk factor of coronary heart disease. The recently identified apolipoprotein A5 (apoA5) is implicated in TG-lowering, which is regulated by peroxisome proliferator-activated receptor-α(PPARα). Statin, a kide of agent influencing PPARα, has been demonstrated to effectively reduce TG, but their mechanisms are poorly understood.ObjectiveThe aim of this study was to investigate the role of apoA5 in the TG-lowering effects of atorvastatin, and to evaluate the mechanisms on apoA5 expression by atorvastatin.MethodsHepG2 cells were incubated in the medium containing various concentrations of atorvastatin (0, 0.05, 0.5, 5.0, 50μM) for 24 hours or incubated with 50μM atorvastatin for different hours(6h, 12h, 18h, 24h).The effects on TG in HepG2 cells by atorvastatin and MK886 were evaluated. The expressions of apoA5 and PPARαwere measured using reverse transcription polymerase chain reaction (RT-PCR) and western blotting (WB) analysis respectively. Results1. Atorvastatin decreased TG levels in a dose- and time-dependent manner in HepG2 cells. Pretreatment of MK886 weakened the effects of atorvastatin on TG(P<0.05).2. Atorvastatin induced apoA5 mRNA and protein in a dose- and time-dependent manner in HepG2 cells. Induction of apoA5 by atorvastatin were notably inhibited by MK886 (P<0.05).3. Atorvastatin increased PPARαmRNA in a dose- and time-dependent manner in HepG2 cells.Conclusion1. TG is associated with apoA5 in HepG2 cells. Increased apoA5 expressions are accompanied by decreased TG levels, which supports apoAV play a key role in down-regulating TG.2. Upregulation of apoA5 expressions by atorvastatin contributes to its hypotriglyceridemic effect in HepG2 cells.3. Atorvastatin possibly induces apoA5 expression in HepG2 cells by upregulation of PPARαexpression.