Up-regulating PPAR-γ expression and NO concentration, and down-regulating PAI-1 concentration in a rabbit atherosclerotic model: the possible antiatherogenic and antithrombotic effects of atorvastatin.

We investigated the effect of atorvastatin on the plasma concentration of plasminogen activator inhibitor-1 (PAI-1) and nitric oxide (NO) in a rabbit model, and the relationship between these effects and peroxisome proliferator-activated receptor γ (PPAR-γ). In our experiments, 24 male Japanese rabbits were divided into 3 groups: the high-cholesterol diet group (the high-C group), the high-cholesterol diet plus atorvastatin group (the atorvastatin group), and the normal diet group (the control group). All rabbits were killed after a 16-week feeding. The expression of PPAR-γ and the plasma concentrations of NO and PAI-1 were evaluated by an immunohistochemical assay while the level of the plasma lipid profile was measured using a commercially available kit. The atorvastatin not only reduces the plasma levels of the total cholesterol (TC) and the low-density lipoprotein cholesterol (LDL-C), but also increases the expression of PPAR-γ and the concentration of NO in comparison to the control group [16.11 ± 2.35% vs 7.68 ± 1.04%; 249.30 ± 27.90 vs 179.12 ± 28.51 (μml/L), p<0.05 respectively]. In addition, the concentration of PAI-1 in the atorvastatin group is lower than that in the control group (0.11 ± 0.01A vs 0.14 ± 0.02A, p<0.05). The changes of PAI-1 and NO in the atorvastatin group are in good accordance to that of PPAR-γ. Results show that atorvastatin significantly up-regulates the expression of nuclear transcription factor, namely PPAR-γ, and induces the changes of the other two factors, which might provide mechanisms for the antiatherosclerotic and antithrombotic effects of atorvastatin.