Ghrelin inhibits post-infarct myocardial remodeling and improves cardiac function through anti-inflammation effect.
Ghrelin is a novel growth hormone-releasing peptide, which has been shown to exert beneficial cardiac effects on chronic heart failure (CHF) recently. In this study, we attempted to investigate the mechanisms for the effect of ghrelin on ventricular remodeling following acute myocardial infarction (MI). Ligation of a coronary artery was used to create an MI in rats. One week after MI, ghrelin (100 microg/kg) or saline was injected subcutaneously twice a day for 4 weeks. When compared to sham groups, ghrelin administration significantly decreased left ventricular (LV) remodeling in post-MI rats, as indicated by increased LV maximum rate of pressure, LV fractional shortening and scar thickness; and decreased LV end-diastolic pressure, LV end-systolic diameter, LV end-diastolic diameter and cardiocytocytes apoptosis. Moreover, ghrelin inhibited the inflammatory response, as shown by decreased mRNA and protein levels of interleukin (IL)-1beta and tumor necrosis factor-alpha (TNF-alpha). Subsequently, the expression of matrix metalloproteinase (MMP)-2 and MMP-9 were also inhibited by ghrelin injection. Ghrelin alleviates LV dysfunction and ventricular remodeling in post-MI rats. This suggests that the beneficial effects of ghrelin on CHF may result from an inhibition of the inflammatory response.
Huang
Cong-Xin
CX
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China. huangcongxin@yahoo.com.cn
Yuan
Ming-Jie
MJ
Huang
He
H
Wu
Gang
G
Liu
Yu
Y
Yu
Sheng-Bo
SB
Li
Hai-Tao
HT
Wang
Tao
T
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D054439:Ghrelin / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009203:Myocardial Infarction / Q000276:immunology*; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D054439:Ghrelin; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9