Ghrelin and Cardiovascular Diseases

Abstract

Ghrelin, a newly discovered bioactive peptide, is a natural endogenous ligand of the growth hormone (GH) secretagogue receptor and initially identified as a strong stimulant for the release of GH. Subsequent research has shown that ghrelin and its various receptors are ubiquitous in many other organs and tissues. Moreover, they participate in the regulation of appetite, energy, bodyweight, metabolism of glucose and fat, as well as modulation of gastrointestinal, cardiovascular, pulmonary, immune functions and cell proliferation/apoptosis. Increasing evidence has demonstrated that ghrelin has a close relationship with cardiovascular system. Ghrelin and its receptors are widely distributed in cardiovascular tissues, and there is no doubt that the effects of ghrelin in the cardiovascular system are mediated not only via its growth-hormone-releasing effect but also by its direct effects on the heart. Exogenous administration of ghrelin can dilate peripheral blood vessels, constrict coronary artery, improve endothelial function, as well as inhibit myocardial cell apoptosis. So, ghrelin may have cardiovascular protective effect, including lowering of blood pressure, regulation of atherosclerosis, and protection from ischemia/reperfusion injury as well as improving the prognosis of myocardial infarction and heart failure. Some of these new functions of ghrelin may provide new potential therapeutic opportunities for ghrelin in cardiovascular medicine. In this paper, we will review the existing evidence for cardiovascular effects of ghrelin, including the cardiovascular function, the variations in ghrelin plasma levels in pathophysiologicalogical conditions, the possible protective mechanisms of ghrelin, as well as its future potential therapeutic roles.

Body composition, appetite-related hormones, adipocytokines, and heart failure in adult patients with congenital heart disease: A preliminary study

“…Even in healthy human volunteers, ghrelin reportedly decreased vascular resistance and increased cardiac index and stroke volume . These results are considered to relate to its vasodilator effects as well as its inhibition of sympathetic activity …”

“…Ghrelin is an orexigenic hormone of gastric origin and is a natural endogenous ligand of the growth hormone (GH) secretagogue receptor that was identified as a stimulant for GH release . Ghrelin and its receptors are ubiquitously expressed in heart and vessels and are considered to regulate appetite, energy, body weight, and metabolism of glucose and fat as well as to modulate gastrointestinal, cardiovascular, pulmonary, immune functions, and cell proliferation/apoptosis by its direct effects and via its role in GH release . In some animal studies, exogenous administration of ghrelin led to the dilatation of peripheral blood vessels, regulation of atherosclerosis, improved endothelial function, and inhibition of myocardial cell apoptos .…”

Somatotropic and cardio-protective effects of ghrelin in experimental models of heart failure: A systematic review

“…Ghrelin plays a cardioprotective role against cardiomyopathy through mechanisms that are independent of GHS-R. Ghrelin increases the size of cardiomyocytes, prevents the activation of cardiac fibrosis, reduces autophagy and prolongs their life. [8,33] It does this by inhibiting the reactive oxygen species and inducing mammalian or mechanistic target of rapamycin that functions in coordinating cell growth and proliferation and also regulates survival of cells. [45] Ghrelin protects the cardiomyocytes against apoptosis, and myocardial injury induced by endoplasmic reticulum stress (ERS) through a GHS-R 1a, Calmodulin-dependent protein kinase kinase (CaMKK) and AMP-activated protein kinase (AMPK) pathway.…”

“…[2][3][4][5][6][7] Ghrelin also has a role in modulation of gastrointestinal, cardiovascular, pulmonary and immune functions, cell proliferation/apoptosis. [8] There is a widespread distribution of ghrelin and its receptors in the cardiovascular tissues. The protective effects of ghrelin on heart are mediated through direct effects on the heart and blood vessel and through.…”

“…[17] Clinical studies have reported that exogenous administration of ghrelin decreases muscle wasting, improves exercise capacity, improves left ventricular (LV) and endothelial function, increase myocardial contractility, dilate peripheral blood vessels, constricts the coronary arteries, reduces blood pressure, inhibits cardiomyocyte apoptosis, inhibit sympathetic nerve activity (SNA) and protects from HF induced by myocardial infarction. [8,[18][19][20][21][22] So also, ghrelin may have other cardiovascular protective effects such as prevention of atherosclerosis as well as protection from ischemia and reperfusion injury. [18,19,23,24] Importantly, administration of ghrelin has been demonstrated to improve the cardiac function and prognosis in patients suffering from end-stage CHF.…”