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

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) x 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) x 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) x 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.