Simvastatin regulates myocardial cytokine expression and improves ventricular remodeling in rats after acute myocardial infarction.
OBJECTIVE
Studies have showed that inflammatory cytokines were involved in the process of left ventricular (LV) remodeling after acute myocardial infarction (AMI), anti-inflammation treatment ameliorated LV remodeling and improved cardiac performance. Hydroxymethylglutary coenzyme A reductase inhibition (statins) could affect the expression of inflammatory cytokines. We hypothesized that statins have beneficial effects on early LV remodeling and cardiac performance in rats with AMI by modulating the production of inflammatory cytokines.


METHODS
Rats with AMI were treated with placebo or simvastatin (gastric gavage) for 4 weeks. The pro-inflammatory cytokines: tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and the anti-inflammatory cytokine: IL-10 excreted by cardiac myocytes was examined. Echocardiography, hemodynamics and collagen type I production were measured to evaluate LV remodeling and cardiac function.


RESULTS
The mRNA expression and protein production of TNF-alpha, IL-1beta, IL-6 and IL-10 in AMI group were significantly elevated compared with sham rats. Simvastatin markedly attenuated the production of TNF-alpha, IL-1beta, IL-6 and increased IL-10 levels in the noninfarcted and infarcted regions, reduced collagen deposition in the noninfarcted myocardium and improved left ventricular function. However simvastatin did not alter plasma lipids.


CONCLUSIONS
Simvastatin ameliorates early LV remodeling and improve cardiac function after AMI. Simultaneously, it decreased pro-inflammatory and increased anti-inflammatory cytokines, which suggests, but does not prove, a causal relationship independent of plasma lipid-lowering effects.
Zhang
Jinying
J
Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
Cheng
Xiang
X
Liao
Yu-Hua
YH
Lu
Baojun
B
Yang
Yali
Y
Li
Bin
B
Ge
Hongxia
H
Wang
Min
M
Liu
Ying
Y
Guo
Zhangqiang
Z
Zhang
Ling
L
D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D016207:Cytokines / Q000235:genetics*; D004195:Disease Models, Animal; D004452:Echocardiography; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007150:Immunohistochemistry; D008055:Lipids / Q000097:blood; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D020257:Ventricular Remodeling / Q000187:drug effects*
D024042:Collagen Type I; D016207:Cytokines; D008055:Lipids; D019821:Simvastatin