Fenofibrate inhibits thrombogenic and fibrinolytic factors expression in adipose tissue of atherosclerotic rabbits

Abstract

Background Tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) activity and/or expression are upregulated in obesity. We investigated TF and PAI-1 mRNA expression in adipose tissues of cholesterol-fed rabbits, and the effects of fenofibrate. Methods Male rabbits were fed either a normal or high-cholesterol diet for 8 weeks. After 4 weeks, those fed high-cholesterol diets were randomly assigned to 30 mg/kg/day fenofibrate and starch. At the end of 12 weeks, subcutaneous adipose was collected. The concentration of TF and PAI-1 mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). The plasma activities of TF and PAI-1 were determined with ELISA and chromogenic substrate method, respectively. Results The atherogenic diet caused a consistent increase in serum concentrations of total cholesterol (TC) ( p<0.05) and did not significantly affect serum triglyceride (TG) concentrations, and increased TF and PAI-1 mRNA expression in adipose tissues (1.149±0.014 and 1.200±0.012, respectively) as compared to the normal diet (1.034±0.011 and 1.098±0.013, respectively) ( p<0.01). The plasma activities of TF [(74.4±28.8) ng/l] and PAI-1 [(15.6±1.9)×10 3 AU/l] in high-cholesterol diet group were higher than those of normal diet group [(33.1±10.7) ng/l and (6.9±0.9)×10 3 AU/l, respectively, p<0.05]. Four-week fenofibrate treatment resulted in significant decrease of TF (1.017±0.010) and PAI-1 mRNA (1.061±0.011, p<0.01), the plasma activity of TF [(40.3±12.2) ng/l, p<0.05] and PAI-1 [(7.5±1.5)×10 3 AU/l, p<0.01] also decreased significantly, and the concentrations of lipids were not changed. Conclusion TF and PAI-1 mRNA expression and plasma activities increased in adipose tissue of cholesterol-fed rabbits. Fenofibrate reduced TF and PAI-1 expression and plasma activity in adipose, suggesting that fenofibrate treatment reduces thrombosis risk, and may have an antithrombotic effect independent of its lipid-lowering.