Fenofibrate inhibits thrombogenic and fibrinolytic factors expression in adipose tissue of atherosclerotic rabbits.
BACKGROUND
Tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) activity and/or expression are upregulated in obesity. We investigated TF and PAI-1 mRNA expression in adipose tissues of cholesterol-fed rabbits, and the effects of fenofibrate.


METHODS
Male rabbits were fed either a normal or high-cholesterol diet for 8 weeks. After 4 weeks, those fed high-cholesterol diets were randomly assigned to 30 mg/kg/day fenofibrate and starch. At the end of 12 weeks, subcutaneous adipose was collected. The concentration of TF and PAI-1 mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). The plasma activities of TF and PAI-1 were determined with ELISA and chromogenic substrate method, respectively.


RESULTS
The atherogenic diet caused a consistent increase in serum concentrations of total cholesterol (TC) (p<0.05) and did not significantly affect serum triglyceride (TG) concentrations, and increased TF and PAI-1 mRNA expression in adipose tissues (1.149+/-0.014 and 1.200+/-0.012, respectively) as compared to the normal diet (1.034+/-0.011 and 1.098+/-0.013, respectively) (p<0.01). The plasma activities of TF [(74.4+/-28.8) ng/l] and PAI-1 [(15.6+/-1.9) x 10(3) AU/l] in high-cholesterol diet group were higher than those of normal diet group [(33.1+/-10.7) ng/l and (6.9+/-0.9) x 10(3) AU/l, respectively, p<0.05]. Four-week fenofibrate treatment resulted in significant decrease of TF (1.017+/-0.010) and PAI-1 mRNA (1.061+/-0.011, p<0.01), the plasma activity of TF [(40.3+/-12.2) ng/l, p<0.05] and PAI-1 [(7.5+/-1.5) x 10(3) AU/l, p<0.01] also decreased significantly, and the concentrations of lipids were not changed.


CONCLUSIONS
TF and PAI-1 mRNA expression and plasma activities increased in adipose tissue of cholesterol-fed rabbits. Fenofibrate reduced TF and PAI-1 expression and plasma activity in adipose, suggesting that fenofibrate treatment reduces thrombosis risk, and may have an antithrombotic effect independent of its lipid-lowering.
Department of Cardiology, The Second XiangYa Hospital of Central South University, Changsha, Hunan 410011, PR China. Zhaosp@medmail.com.cn
Shui-Ping
SP
Zhao
Jieqi
J
Li
Zhumei
Z
Xu
Jie
J
Wu
Quanzhong
Q
Li
Huijun
H
Ye
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000494:pharmacology; D004032:Diet; D004797:Enzyme-Linked Immunosorbent Assay; D011345:Fenofibrate / Q000494:pharmacology*; D005342:Fibrinolysis / Q000187:drug effects*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013925:Thromboplastin / Q000494:pharmacology
D002791:Cholesterol, Dietary; D000960:Hypolipidemic Agents; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D013925:Thromboplastin; D002784:Cholesterol; D011345:Fenofibrate