Mechanisms of Ghrelin anti-heart failure: inhibition of Ang II-induced cardiomyocyte apoptosis by down-regulating AT1R expression

• Published in: PloS one 2014-01, Vol.9 (1), p.e85785
• Main Authors: Yang, Chunyan, Liu, Zhonghui, Liu, Kai, Yang, Ping
• Format: Article
• Language: English
• Subjects: Analysis; Angiotensin; Angiotensin II; Angiotensin II - pharmacology; Angiotensins; Animals; Apoptosis; Apoptosis - drug effects; Biology; Cardiology; Cardiomyocytes; Case-Control Studies; Caspase; Caspase 3 - metabolism; Caspase-3; Coronary artery; Down-Regulation - drug effects; Enzyme-linked immunosorbent assay; Ethics; Female; Ghrelin; Ghrelin - metabolism; Ghrelin - pharmacology; Growth hormone; Growth hormones; Heart; Heart attacks; Heart diseases; Heart failure; Heart Failure - enzymology; Heart Failure - pathology; Heart Failure - prevention & control; Hospitals; Humans; Ischemia; Laboratory animals; Ligands; Male; Medicine; Metabolism; Middle Aged; Musculoskeletal system; Myocardium - enzymology; Myocardium - pathology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Neonates; Patients; Peptides; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Receptor, Angiotensin, Type 1 - genetics; Receptor, Angiotensin, Type 1 - metabolism; Receptor, Angiotensin, Type 2 - genetics; Receptor, Angiotensin, Type 2 - metabolism; Receptors; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Serum levels; Somatotropin; Studies
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0085785

Ghrelin is a novel growth hormone-releasing peptide administered to treat chronic heart failure (CHF). However, the underlying mechanism of its protective effects against heart failure (HF) remains unclear. A total of 68 patients with CHF and 20 healthy individuals were included. The serum levels of Angiotensin II (Ang II) and ghrelin were measured using ELISA. The results showed that Ang II and ghrelin were both significantly increased in CHF patients and that the ghrelin levels were significantly positively correlated with Ang II. The left anterior descending coronary artery was ligated to establish a rat model of CHF, and cultured cardiomyocytes from neonatal rats were stimulated with Ang II to explore the role of ghrelin in CHF. The results showed that ghrelin inhibited cardiomyocyte apoptosis both in vivo and in vitro. Furthermore, caspase-3 expression was examined, and the results revealed that Ang II induces cardiomyocyte apoptosis through the caspase-3 pathway, whereas ghrelin inhibits this action. Lastly, to further elucidate the mechanism by which ghrelin inhibits Ang II action, the expression of the AT1 and AT2 receptors was evaluated; the results showed that Ang II up-regulates the AT1 and AT2 receptors in cardiomyocytes, whereas ghrelin inhibits AT1 receptor up-regulation but does not affect AT2 receptor expression. These data suggest that the serum levels of ghrelin are significantly positively correlated with Ang II in CHF patients and that ghrelin can inhibit Ang II-induced cardiomyocyte apoptosis by down-regulating AT1R, thereby playing a role in preventing HF.