BACKGROUND: We have recently demonstrated that tissue factor (TF) expression increases in adipose tissues/adipocytes of cholesterol-fed rabbit, which is associated with a hypercoagulable state that contributes to thrombosis. In this study, we evaluated the ability of atorvastatin to modulate TF expression in cholesterol-fed rabbit and the regulatory mechanism. METHODS: Male rabbits were randomly fed with normal diet and high-cholesterol diet for 8 weeks, following 4 weeks, those fed high-cholesterol diet were randomly assigned to atorvastatin or starch. At the end of 12 weeks, subcutaneous adipose was collected, and culture adipocyte. TF mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). TF concentrations were determined with ELISA. The in vitro effect of atorvastatin and mevalonate (MVA) on TF production in adipocytes was observed. RESULTS: Atorvastatin reduced serum TC and LDL-C levels (P<0.05), and decreased plasma TF concentration and expression in adipose tissues/adipocytes from cholesterol-fed rabbits. In vitro, atorvastatin dose-dependently suppressed TF expression and protein secretion in adipocytes. MVA reversed the inhibitory effect of atorvastatin on TF expression in concentration-dependent manner. CONCLUSIONS: Results provide further support for the antithrombotic effect of atorvastatin. It also indicated that mevalonate pathway may play an important role in TF expression in adipocyte.
BACKGROUND: We have recently demonstrated that tissue factor (TF) expression increases in adipose tissues/adipocytes of cholesterol-fed rabbit, which is associated with a hypercoagulable state that contributes to thrombosis. In this study, we evaluated the ability of atorvastatin to modulate TF expression in cholesterol-fed rabbit and the regulatory mechanism. METHODS: Male rabbits were randomly fed with normal diet and high-cholesterol diet for 8 weeks, following 4 weeks, those fed high-cholesterol diet were randomly assigned to atorvastatin or starch. At the end of 12 weeks, subcutaneous adipose was collected, and culture adipocyte. TF mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). TF concentrations were determined with ELISA. The in vitro effect of atorvastatin and mevalonate (MVA) on TF production in adipocytes was observed. RESULTS:Atorvastatin reduced serum TC and LDL-C levels (P<0.05), and decreased plasma TF concentration and expression in adipose tissues/adipocytes from cholesterol-fed rabbits. In vitro, atorvastatin dose-dependently suppressed TF expression and protein secretion in adipocytes. MVA reversed the inhibitory effect of atorvastatin on TF expression in concentration-dependent manner. CONCLUSIONS: Results provide further support for the antithrombotic effect of atorvastatin. It also indicated that mevalonate pathway may play an important role in TF expression in adipocyte.