Fenofibrate inhibits thrombogenic and fibrinolytic factors expression in adipose tissues

Objective:The purpose of this study was to investigate tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) mRNA expression in adipose tissues of atherosclerotic rabbits, and the effects of fenofibrate. Method:Male rabbits (n=15) were randomly fed with normal diet (control group) and high-cholesterol diet for 8 weeks, following 4 weeks, those fed high-cholesterol diets were randomly assigned to receive fenofibrate (30 mg·kg -1 ·d -1 treatment group) or placebo (atherosclerotic group). At the end of 12 th week from the start of experiment, subcutaneous adipose tissues were collected under deep anesthesia. The levels of TF and PAI-1 mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR). The plasma TF and PAI-1 activities were determined by ELISA and chromogenic substrate assay, respectively. Result:The atherogenic diet caused a consistent increase in serum levels of total cholesterol (TC) (P0.05) and did not affect serum triglyceride (TG) levels. Fenofibrate did not change serum levels of TG and TC. In atherosclerotic group, TF and PAI-1 mRNA expression levels in adipose tissues (1.15±0.01 and 1.20±0.01, respectively), were significantly higher than those in control group (1.03±0.01 and 1.10±0.01, respectively) (P0.01); the plasma activities of TF and PAI-1 (74.4±28.8)ng/L and [15.6±1.9]×10 3AU/L, respectively) were higher than those in control group ([33.1±10.7]ng/L and [6.9±0.9]×10 3AU/L, respectively) (P0.05). After treatment with fenofibrate, TF and PAI-1 mRNA expression levels (1.02±0.01 and 1.06±0.01, respectively), the plasma activities of TF and PAI-1 ([40.3±12.2]ng/L and [7.5±1.5]×10 3AU/L, respectively) were lower than those in atherosclerotic group (P0.01 and P0.05, respectively). Conclusion:TF and PAI-1 mRNA expression increases in adipose tissues of atherosclerotic rabbit, and the plasma activity of TF and PAI-1 also increase. Fenofibrate reduces TF and PAI-1 expression in adipose tissues, and degrades the plasma activity of TF and PAI-1, suggesting that fenofibrate may have an antithrombtic effect independent of its lipid-lowering.