Atorvastatin reduces tissue factor expression in adipose tissue of atherosclerotic rabbits

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 highcholesterol 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 antithrombfic effect of atorvastatin. It also indicated that mevalonate pathway may play an important role in TF expression in adipocyte. (c) 2006 Elsevier Ireland Ltd. All rights reserved.