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 gamma (PPAR-gamma). 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-gamma 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-gamma 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 (mu ml/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-gamma. Results show that atorvastatin significantly up-regulates the expression of nuclear transcription factor, namely PPAR-gamma, and induces the changes of the other two factors, which might provide mechanisms for the antiatherosclerotic and antithrombotic effects of atorvastatin. (C) 2008 Published by Elsevier Ireland Ltd.
[1]Jilin Univ, China Japan Union Hosp, Dept Cardiol, Changchun 130033, Peoples R China.
[2]Chinese Acad Med Sci, Dept Cardiol, Fu Wai Hosp, Beijing 100037, Peoples R China.
[3]Jilin Univ, Dept Cardiol, Hosp 1, Changchun 130021, Peoples R China.
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