title: Cardiovascular actions of the ghrelin gene-derived peptides and growth hormone-releasing hormone.
abstract: In 1976, small peptide growth hormone secretagogues (GHSs) were discovered and found to promote growth hormone (GH) release from the pituitary. The GHS receptor (GHS-R) was subsequently cloned, and its endogenous ligand ghrelin was later isolated from the stomach. Ghrelin is a 28-amino acid peptide, whose acylation is essential for binding to GHS-R type 1a and for the endocrine functions, including stimulation of GH secretion and subsequent food intake. Unacylated ghrelin, the other ghrelin form, although devoid of GHS-R binding is an active peptide, sharing many peripheral effects with acylated ghrelin (AG). The ghrelin system is broadly expressed in myocardial tissues, where it exerts different functions. Indeed, ghrelin inhibits cardiomyocyte and endothelial cell apoptosis, and improves left ventricular (LV) function during ischemia-reperfusion (I/R) injury. In rats with heart failure (HF), ghrelin improves LV dysfunction and attenuates the development of cardiac cachexia. Similarly, ghrelin exerts vasodilatory effects in humans, improves cardiac function and decreases systemic vascular resistance in patients with chronic HF. Obestatin is a recently identified ghrelin gene peptide. The physiological role of obestatin and its binding to the putative GPR39 receptor are still unclear, although protective effects have been demonstrated in the pancreas and heart. Similarly to AG, the hypothalamic peptide growth hormone-releasing hormone (GHRH) stimulates GH release from the pituitary, through binding to the GHRH-receptor. Besides its proliferative effects in different cell types, at the cardiovascular level GHRH inhibits cardiomyocyte apoptosis, and reduces infarct size in both isolated rat heart after I/R and in vivo after myocardial infarction. Therefore, both ghrelin and GHRH exert cardioprotective effects, which make them candidate targets for therapeutic intervention in cardiovascular dysfunctions.
authors.affiliation: Laboratory of Molecular and Cellular Endocrinology, Division of Endocrinology, Diabetology and Metabolism, Department of Internal Medicine, University of Turin, Italy. riccarda.granata@unito.it
authors.forename: Riccarda
authors.initials: R
authors.lastname: Granata
authors.forename: Jörgen
authors.initials: J
authors.lastname: Isgaard
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Alloatti
authors.forename: Ezio
authors.initials: E
authors.lastname: Ghigo
mesh_terms: D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D054439:Ghrelin / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D054439:Ghrelin; D013007:Growth Hormone-Releasing Hormone