Atorvastatin reduces plasminogen activator inhibitor-1 expression in adipose tissue of atherosclerotic rabbits

• Published in: Clinica chimica acta 2006-08, Vol.370 (1), p.57-62
• Main Authors: Li, Jie-Qi, Zhao, Shui-Ping, Li, Quan-Zhong, Cai, Yun-Chang, Wu, Li-Rong, Fang, Ying, Li, Ping
• Format: Article
• Language: English
• Subjects: Adipose Tissue - drug effects; Adipose Tissue - metabolism; Adipose tissue/adipocyte; Animal Feed; Animals; Atherosclerosis; Atherosclerosis - genetics; Atherosclerosis - metabolism; Atorvastatin; Atorvastatin Calcium; Cholesterol - blood; Cholesterol - pharmacology; Fibrinolysis; Gene Expression Regulation; Heptanoic Acids - pharmacology; Male; Mevalonate; Mevalonic Acid - pharmacology; Plasminogen Activator Inhibitor 1 - genetics; Plasminogen Activator Inhibitor 1 - metabolism; Plasminogen activator inhibitor-1; Pyrroles - pharmacology; Rabbits; RNA, Messenger - genetics; Triglycerides - blood
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2006.01.024

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 inhibitory effect of atorvastatin on PAI-1 expression in concentration-dependent manner. Atorvastatin reduces plasma PAI-1 concentration and PAI-1 expression in adipose tissue and adipocyte of atherosclerotic rabbit, and inhibits PAI-1 expression and protein secretion in adipocytes in vitro, suggesting that it may have an antithrombtic effect. We also suggest that the mevalonate pathway may play an important role in PAI-1 expression in adipocyte.