In rats with myocardial infarction, interference by simvastatin with the TLR4 signal pathway attenuates ventricular remodelling.
OBJECTIVE
The objective of this study was to investigate the effect of simvastatin on TLR4,TNF-alpha and IL-6 expression in the myocardium and its relation to left ventricular (LV) remodelling in a rat model of myocardial infarction (MI) and to investigate the mechanism by which simvastatin improves LV remodelling in rats after MI.


RESULTS
The rat MI models were established by ligation of the left anterior descending coronary artery and divided into three groups: (I) an untreated MI group; (2) a group treated with simvastatin [40 mg/(kg/d)] for 4 weeks; (3) the sham group. Cardiac geometry and function were determined by echocardiography and infarct size was determined by the histomorphometric analysis; the expression ofTLR4 in the myocardium was measured by RT-PCR and western blotting;TNF-alpha and IL-6 levels in myocardial homogenate and serum were measured by ELISA. LVEDD and LVESD significantly increased and fractional shortening (FS) markedly decreased in the MI group. It was clear that simvastatin inhibited LV dilation and improved LV function after MI without affecting infarct size. The expression of TLR4, TNF-alpha and IL-6 in the myocardium significantly increased in the MI group and simvastatin markedly inhibits the expression of TLR4, TNF-alpha, and IL-6 in the myocardium after MI. Serum TNF-alpha and IL-6 levels between the MI group and the simvastatin group remained unchanged. Both in the MI group and the simvastatin group,TLR4 protein positively related to LVEDD and to the levels of TNF-alpha and IL-6 in the myocardium, respectively.


CONCLUSIONS
Amelioration of LV remodelling in rats after MI by simvastatin might be associated with its effect on the TLR4-mediated signalling pathway in the myocardium.
Sheng
Fu-qiang
FQ
Department of Cardiology, Affiliated Taihe Hospital, Yunyang Medical College, Shiyan, Hubei. shengfq1129@hotmail.com
Xu
Rong
R
Cheng
Long-xian
LX
Zeng
Qiu-tang
QT
Gao
Wen
W
Wang
Wei
W
Dang
Shu-yi
SY
Wang
Chong-quan
CQ
He
Chao-rong
CR
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D004108:Dilatation, Pathologic; D004730:Endothelium, Vascular / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D019821:Simvastatin / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology*
D000924:Anticholesteremic Agents; D018840:HSP70 Heat-Shock Proteins; D015850:Interleukin-6; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D019821:Simvastatin