title: Metabolic and cardiovascular effects of ghrelin.
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.
authors.affiliation: Department of Medicina Interna, Università di Tor Vergata, 00133 Rome, Italy.
authors.forename: Manfredi
authors.initials: M
authors.lastname: Tesauro
authors.forename: Francesca
authors.initials: F
authors.lastname: Schinzari
authors.forename: Miriam
authors.initials: M
authors.lastname: Caramanti
authors.forename: Renato
authors.initials: R
authors.lastname: Lauro
authors.forename: Carmine
authors.initials: C
authors.lastname: Cardillo
references.citation: J Cell Biol. 2002 Dec 23;159(6):1029-37
references.pmid: 12486113
references.citation: Am J Physiol Regul Integr Comp Physiol. 2001 May;280(5):R1483-7
references.pmid: 11294772
references.citation: Circulation. 2004 Dec 14;110(24):3674-9
references.pmid: 15569841
references.citation: J Biol Chem. 2002 Feb 15;277(7):5667-74
references.pmid: 11724768
references.citation: Nat Med. 2002 Jul;8(7):643-4
references.pmid: 12091883
references.citation: Circulation. 2005 Nov 8;112(19):2986-92
references.pmid: 16260640
references.citation: Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6320-5
references.pmid: 18443287
references.citation: Front Neuroendocrinol. 2004 Apr;25(1):27-68
references.pmid: 15183037
references.citation: Cardiovasc Hematol Disord Drug Targets. 2008 Jun;8(2):133-7
references.pmid: 18537600
references.citation: Endocrinology. 2006 May;147(5):2306-14
references.pmid: 16484324
references.citation: Circulation. 2001 Sep 18;104(12):1430-5
references.pmid: 11560861
references.citation: Am J Physiol Endocrinol Metab. 2005 Mar;288(3):E486-92
references.pmid: 15507538
references.citation: J Pediatr. 2004 Jan;144(1):36-42
references.pmid: 14722516
references.citation: J Clin Endocrinol Metab. 2000 Oct;85(10):3803-7
references.pmid: 11061542
references.citation: Endocr Rev. 2004 Jun;25(3):426-57
references.pmid: 15180951
references.citation: J Clin Endocrinol Metab. 2001 Dec;86(12):5854-9
references.pmid: 11739451
references.citation: J Clin Endocrinol Metab. 2002 Jan;87(1):240-4
references.pmid: 11788653
references.citation: Rev Endocr Metab Disord. 2006 Dec;7(4):237-49
references.pmid: 17195943
references.citation: Nature. 1999 Dec 9;402(6762):656-60
references.pmid: 10604470
references.citation: Proc Nutr Soc. 2008 Aug;67(3):263-9
references.pmid: 18452642
references.citation: J Clin Endocrinol Metab. 2002 Dec;87(12):5625-9
references.pmid: 12466363
references.citation: Am J Physiol Heart Circ Physiol. 2008 Jan;294(1):H426-32
references.pmid: 18024547
references.citation: Nat Med. 2009 Jul;15(7):741-5
references.pmid: 19503064
references.citation: Gut. 2005 Jan;54(1):18-24
references.pmid: 15591499
references.citation: J Clin Endocrinol Metab. 2002 Jun;87(6):2988
references.pmid: 12050285
references.citation: J Endocrinol. 2003 Nov;179(2):237-44
references.pmid: 14596675
references.citation: J Clin Endocrinol Metab. 2001 Apr;86(4):1738-45
references.pmid: 11297611
references.citation: Gastroenterology. 2005 Jul;129(1):8-25
references.pmid: 16012930
references.citation: J Clin Invest. 2004 Jul;114(1):57-66
references.pmid: 15232612
references.citation: Br J Pharmacol. 2002 Aug;136(8):1146-52
references.pmid: 12163347
references.citation: Diabetes. 2003 Oct;52(10):2546-53
references.pmid: 14514639
references.citation: Endocrinology. 2004 Jan;145(1):234-42
references.pmid: 14551228
references.citation: J Clin Endocrinol Metab. 2001 Feb;86(2):881-7
references.pmid: 11158061
references.citation: J Clin Endocrinol Metab. 2002 Mar;87(3):1300-8
references.pmid: 11889202
references.citation: J Clin Endocrinol Metab. 2003 Apr;88(4):1537-42
references.pmid: 12679436
references.citation: Diabetes. 2001 Apr;50(4):707-9
references.pmid: 11289032
references.citation: J Endocrinol Invest. 2006 Feb;29(2):115-21
references.pmid: 16610236
references.citation: Metabolism. 2005 Jul;54(7):925-9
references.pmid: 15988702
references.citation: Endocrinology. 2008 Feb;149(2):827-35
references.pmid: 18039782
references.citation: J Endocrinol Invest. 2001 Mar;24(3):RC7-9
references.pmid: 11314756
references.citation: Mol Endocrinol. 1997 Apr;11(4):415-23
references.pmid: 9092793
references.citation: Curr Opin Pharmacol. 2006 Apr;6(2):142-7
references.pmid: 16483844
references.citation: N Engl J Med. 2002 May 23;346(21):1623-30
references.pmid: 12023994
references.citation: Vitam Horm. 2008;77:207-38
references.pmid: 17983858
references.citation: Metabolism. 2003 Nov;52(11):1460-3
references.pmid: 14624407
references.citation: Cardiovasc Res. 2004 Jun 1;62(3):481-8
references.pmid: 15158140
references.citation: J Clin Endocrinol Metab. 2005 Dec;90(12):6448-53
references.pmid: 16204363
references.citation: Am J Physiol Endocrinol Metab. 2007 Mar;292(3):E756-64
references.pmid: 17106060
references.citation: Trends Endocrinol Metab. 2001 Apr;12(3):118-22
references.pmid: 11306336
references.citation: Endocrinology. 2003 Dec;144(12):5184-7
references.pmid: 14525914
references.citation: J Biol Chem. 2005 Jul 1;280(26):25196-201
references.pmid: 15899896
references.citation: Cardiovasc Res. 2006 Jan;69(1):227-35
references.pmid: 16226234
references.citation: FEBS Lett. 2003 Sep 25;552(2-3):105-9
references.pmid: 14527669
references.citation: Endokrynol Pol. 2008 May-Jun;59(3):207-11
references.pmid: 18615394
references.citation: Circulation. 2001 Oct 23;104(17):2034-8
references.pmid: 11673342
references.citation: Endocrinology. 2003 Mar;144(3):754-9
references.pmid: 12586750
references.citation: Clin Endocrinol (Oxf). 2005 Jan;62(1):1-17
references.pmid: 15638864
references.citation: Regul Pept. 2003 Nov 15;116(1-3):101-7
references.pmid: 14599721
references.citation: Hypertension. 2009 Nov;54(5):995-1000
references.pmid: 19786648
references.citation: Nature. 2000 Oct 19;407(6806):908-13
references.pmid: 11057670
references.citation: J Med Chem. 2000 Nov 16;43(23):4370-6
references.pmid: 11087562
references.citation: Trends Endocrinol Metab. 2006 Jan-Feb;17(1):13-8
references.pmid: 16309920
references.citation: J Endocrinol Invest. 2005;28(5 Suppl):23-5
references.pmid: 16114271
references.citation: J Endocrinol. 2002 Oct;175(1):201-9
references.pmid: 12379504
references.citation: Mol Interv. 2002 Dec;2(8):494-503
references.pmid: 14993401
references.citation: Basic Res Cardiol. 2003 Nov;98(6):401-5
references.pmid: 14556085
references.citation: Cell. 2008 Feb 8;132(3):387-96
references.pmid: 18267071
references.citation: Regul Pept. 2005 Aug 15;130(1-2):97-103
references.pmid: 15946750
references.citation: Intern Med. 2006;45(3):127-34
references.pmid: 16508225
references.citation: Br J Pharmacol. 2001 Sep;134(1):143-9
references.pmid: 11522606
references.citation: Circulation. 2004 May 11;109(18):2221-6
references.pmid: 15117840