A novel peptide ghrelin inhibits neural remodeling after myocardial infarction in rats

• Published in: European journal of pharmacology Vol. 618; no. 1; pp. 52 - 57
• Main Authors: Yuan, Ming-Jie, Huang, Cong-Xin, Tang, Yan-Hong, Wang, Xi, Huang, He, Chen, Yong-Jun, Wang, Tao
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15.09.2009; Elsevier
• Subjects: Animals; Biological and medical sciences; Cardiac neural remodeling; Cardiology. Vascular system; Coronary heart disease; Endothelin-1 - genetics; Gene Expression Regulation - drug effects; Ghrelin; Ghrelin - pharmacology; Heart; Inflammation - metabolism; Inflammation response; Interleukin-1beta - genetics; Male; Medical sciences; Myocardial infarction; Myocardial Infarction - metabolism; Myocardial Infarction - physiopathology; Myocarditis. Cardiomyopathies; Nerve growth factor; Nerve Growth Factor - genetics; Nerve Growth Factor - metabolism; NF-kappa B - metabolism; Pharmacology. Drug treatments; Protein Transport - drug effects; Rats; Rats, Sprague-Dawley; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal Transduction - drug effects; Sympathetic Nervous System - drug effects; Sympathetic Nervous System - metabolism; Sympathetic Nervous System - physiopathology; Tumor Necrosis Factor-alpha - genetics; Myocardial infarction; Nerve growth factor; Ghrelin; Cardiac neural remodeling; Inflammation response; Heart; Peptides; Rat; Rodentia; Cardiovascular disease; Inflammation; Coronary heart disease; Myocardial disease; Appetite stimulant; Vertebrata; Mammalia; Animal; Circulatory system
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2009.07.015

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 µg/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-κBp65 protein and I-κBα 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-1β, tumor necrosis factor-α, and endothelin-l mRNA expression, and inhibited NF-κB 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.