Abstract
Plasminogen activator inhibitor-1 (PAI-1) expression are increased in adipose tissues/adipocytes of obese mice, which is associated with a hypofibrinolytic state that contributes to thrombosis. We recently demonstrated that PAI-1 expression increases in adipose tissues/adipocytes of cholesterol-fed rabbits. In this study, we evaluated the ability of atorvastatin to modulate PAI-1 expression in cholesterol-fed rabbits and the regulatory mechanism. 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 2.5 mg/kg/day atorvastatin or starch. At the end of 12 weeks, subcutaneous adipose was collected, and culture adipocyte. PAI-1 mRNA was detected by RT-PCR. PAI-1 concentrations were determined with ELISA. The effect of atorvastatin and mevalonate (MVA) on PAI-1 production in adipocytes in vitro was observed. Atorvastatin significantly reduced serum TC and LDL-C concentrations (p<0.05), and decreased plasma PAI-1 concentration and PAI-1 expression in adipose tissues/adipocytes from cholesterol-fed rabbits. In vitro, atorvastatin dose-dependently suppressed PAI-1 expression and protein secretion in adipocytes. MVA reversed the...Continue Reading
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