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


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 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.


RESULTS
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.


CONCLUSIONS
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.
Li
Jie-Qi
JQ
Department of Cardiology, The Affiliated Hospital of GuiYang Medical College, Guiyang, Guizhou 550004, PR China. jieqili@hotmail.com
Zhao
Shui-Ping
SP
Li
Quan-Zhong
QZ
Cai
Yun-Chang
YC
Wu
Li-Rong
LR
Fang
Ying
Y
Li
Ping
P
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism*; D000821:Animal Feed; D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism*; D000069059:Atorvastatin; D002784:Cholesterol / Q000097:blood / Q000494:pharmacology; D005786:Gene Expression Regulation; D006538:Heptanoic Acids / Q000494:pharmacology*; D008297:Male; D008798:Mevalonic Acid / Q000494:pharmacology; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D014280:Triglycerides / Q000097:blood
D006538:Heptanoic Acids; D017395:Plasminogen Activator Inhibitor 1; D011758:Pyrroles; D012333:RNA, Messenger; D014280:Triglycerides; D002784:Cholesterol; D000069059:Atorvastatin; D008798:Mevalonic Acid