Abstract
Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is synthesized as a preprohormone and then proteolytically processed to yield a 28-amino acid peptide. This peptide was originally reported to induce growth hormone release; large evidence, however, has indicated many other physiological activities of ghrelin, including regulation of food intake and energy balance, as well as of lipid and glucose metabolism. Ghrelin receptors have been detected in the hypothalamus and the pituitary, but also in the cardiovascular system, where ghrelin exerts beneficial hemodynamic activities. Ghrelin administration acutely improves endothelial dysfunction by increasing nitric oxide bioavailability and normalizes the altered balance between endothelin-1 and nitric oxide within the vasculature of patients with metabolic syndrome. Other cardiovascular effects of ghrelin include improvement of left ventricular contractility and cardiac output, as well as reduction of arterial pressure and systemic vascular resistance. In addition, antinflammatory and antiapoptotic actions of ghrelin have been reported both in vivo and in vitro. This review summarizes the most recent findings on the metabolic and cardiovascular effects of ghrelin through GH-dependent and -independent mechanisms and the possible role of ghrelin as a therapeutic molecule for treating cardiovascular diseases.
Highlights
A 28-amino-acid peptide hormone mainly secreted by the X/A-like cells in the oxyntic mucosa of the stomach, has been discovered as the endogenous ligand of the orphan receptor growth hormone secretagogues 1a (GHS-R1a) [1]
Two major forms of ghrelin are found in tissues and plasma: n-octanoyl-modified ghrelin and des-acyl ghrelin [7]; ghrelin is the first known secreted bioactive peptide in mammals modified by an acyl acid on its third serine residues through the recently discovered enzyme ghrelin O-acyl transferase (GOAT) [8,9,10]
These results suggest that ghrelin could improve muscle wasting in patients with chronic heart failure and cardiac cachexia, a severe catabolic state characterized by weight loss and muscle wasting, resistant to long-term treatment with nutritional supplements
Summary
A 28-amino-acid peptide hormone mainly secreted by the X/A-like cells in the oxyntic mucosa of the stomach, has been discovered as the endogenous ligand of the orphan receptor growth hormone secretagogues 1a (GHS-R1a) [1]. Two major forms of ghrelin are found in tissues and plasma: n-octanoyl-modified ghrelin and des-acyl ghrelin [7]; ghrelin is the first known secreted bioactive peptide in mammals modified by an acyl acid on its third serine residues through the recently discovered enzyme ghrelin O-acyl transferase (GOAT) [8,9,10] This postranslational modification is essential for binding to the GHS-R 1a and for several ghrelin biological activities, including the GH-releasing capacity and the actions on the endocrine axis, on energy balance and glucose homeostasis [3]. Ghrelin plasma levels are mainly regulated by nutritional and metabolic factors; they are increased by energy restriction (such as malnutrition, anorexia nervosa, and cachexia) and decreased by food intake and overfeeding [18] These notions are in agreement with several studies showing reduced circulating ghrelin in patients with obesity and metabolic syndrome [19, 20]. Chronic ghrelin administration increases body weight, adiposity, and the expression of uncoupling protein (UCP) mRNA in brown and white adipose tissue in mice [39]
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