A novel peptide ghrelin inhibits neural remodeling after myocardial infarction in rats.
Ghrelin is a newly discovered peptide as an endogenous ligand for the growth hormone secretagogue receptor, and has been demonstrated to exert beneficial effect in the cardiovascular system. In the present study, we investigated whether ghrelin administration could inhibit cardiac neural remodeling and sympathetic hyperinnervation after myocardial infarction. Sprague-Dawley rats underwent coronary ligation to induce myocardial infarction and receiving ghrelin chronically (100 microg/kg s.c., twice daily) or saline control for 4 weeks after onset of ischemia. Four weeks after treatment, rats were sacrificed. We examined the expression of nerve growth factor and never markers as well as the mRNA expressions of inflammatory mediators in the infarcted border and non-infarcted left ventricular free wall. We also examined the NF-kappaBp65 protein and I-kappaBalpha protein levels by Western blot analysis. Compared to the control group, ghrelin administration significantly decreased the density of nerve fibers with positive immunostaining for GAP43 and TH, and decreased NGF mRNA and protein levels in the infarcted border and the non-infarcted area. Ghrelin also significantly suppressed interleukin-1beta, tumor necrosis factor-alpha, and endothelin-l mRNA expression, and inhibited NF-kappaB activation. In conclusion, treatment with ghrelin inhibited neural remodeling and sympathetic hyperinnervation, the process that may be associated with the inhibition of proinflammatory response and NGF signaling.
Yuan
Ming-Jie
MJ
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China.
Huang
Cong-Xin
CX
Tang
Yan-Hong
YH
Wang
Xi
X
Huang
He
H
Chen
Yong-Jun
YJ
Wang
Tao
T
D000818:Animals; D019332:Endothelin-1 / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D054439:Ghrelin / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology*; D016328:NF-kappa B / Q000378:metabolism; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D019332:Endothelin-1; D054439:Ghrelin; D053583:Interleukin-1beta; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D020932:Nerve Growth Factor