The New Trends in Physiological and Pathological Actions of Ghrelin (Brain-Heart Axis) on the Heart and Cardiovascular System
Main Article Content
Abstract
Background: Ghrelin increased significantly the Left Ventriculus Eject Fraction and end-systolic volume after 30 minutes of intra-venous injection and without alterations heart rate and blood pressure.
Ghrelin was discovered in 1999 as an only one 28 amino acid peptides (with octanoyl serine group) located on the short arm of chromosome 3 (position 3p25-26) having six exons, two are noncoding and four introns and encodes a 511 bp mRNA.
Ghrelin is synthesized by the endocrine X/A-like cells located from the gastric fundus mucosa through the whole mucosa of the medium right vertical side of the stomach until to the 1 inch before anatomical pylorus. These cells are responsible to produced 80% of the whole ghrelin produced in the human body. Furthermore, other place of this production occurs at the hypothalamus, the pituitary, second portion of duodenum, pancreas, heart and other tissues. Bibliographic references also demonstrate the importance of ghrelin’s action in the main cardiovascular activities.
Related to cardiovascular activities, ghrelin plays multitudinous beneficial and thereby help during cardiovascular diseases. Several studies demonstrated that ghrelin cause an anti-inflammatory activity by the inhibition of proinflammatory cytokines which can diminish inflammatory diseases in the heart, pericardium and specific innervations, for instance, vagus nerve and inhibited sympathetic nerves. Outcomes of this review emphasize these important actions of ghrelin.
Methods: A systematic review of ghrelin activities over the heart and cardiovascular system with the inclusion of papers in review involved the physiological and physio pathological activities of ghrelin in vivo and in vitro studies.
Results: Ghrelin is a natural tide with the growth hormone secretagogue (GHS) receptor (GHS-R) which cloned in 1996. The processes which generate this peptide and ghrelin-related peptides are transcriptional, translational and posttranslational. Homo and heterodimers of GHS-R and other yet unidentified receptors mediate the biological actions of acyl ghrelin and desacyl ghrelin. However, the main biological functions of ghrelin involve the secretion of growth hormone, stimulation of appetite and food intake at the hypothalamus, modulate acid secretion and motility, endocrine and exocrine pancreas secretion, blockaded insulin activity, heart functions and cardiovascular responses and other.
Conclusion: One of the main occurrences in acute heart infarction is an increase activation of cardiac sympathetic nerve activity (CSNA) which is one of the causes of chronic cardiac dysfunction (CCD). Ghrelin is an effective for obtain a better cardiac function and by the suppression of renal sympathetic nerve activity which also have an important benefit to the acute myocardial infarction.
Therefore, the physiological effects of ghrelin are very important to the body homeostasis even in the grave heart and cardiovascular diseases and in the immunological system.
Keywords:
Ghrelin, growth hormone, receptors, heart failure
Article Details
How to Cite
PIROLLA, Eduardo Henrique; MACCAPANI, Gabriel Naman.
The New Trends in Physiological and Pathological Actions of Ghrelin (Brain-Heart Axis) on the Heart and Cardiovascular System.
Medical Research Archives, [S.l.], v. 12, n. 8, aug. 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/5524>. Date accessed: 06 sep. 2024.
doi: https://doi.org/10.18103/mra.v12i8.5524.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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3. Rizzo M, Rizvi A A, Sudar E et al. A review of the cardiovascular and anti-atherogenic effects of ghrelin. Current Pharm Design, 2013; 19: 4953-4963.
4. Pirolla H P et cols. A Modified laparoscopic sleeve gastrectomy for the treatment of diabetes mellitus type 2 and metabolic syndrome in obesity. Am J Surg 2012; Jun;203(6):785-92.
5. Kishimoto I, Tokudome T, Hosoda H, et al. Ghrelin and cardiovascular diseases. In: Kastin AJ, editor. Handbook of the Biologically Active Peptides. 2012
6. Huda MS, Mani H, Dovey T, Halford JC, Boyland E, Daousi C, Wilding JP, Pinkney J. Ghrelin inhibits autonomic function in healthy controls, but has no effect on obese and vagotomized subjects. Clin Endocrinol (Oxf) 2010;73:678—85
7. Smith RG, Cheng K, Schoen WR, Pong SS, Hickey G, Jacks T. A nonpeptidyl growth hormone secretagogue. Science 1993;260(2):1640—3.
8. Howard AD, Fieghner SD, Cully DF, Arena JP, Liberator PA, Rosenblum CI. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 1996;273:974—7.
9. Kojima M, Kangawa K. drug insight: the functions of ghrelin and its potential as a multitherapeutic hormone.Nat Clin Pract Endocrinol Metab 2006;2:80—8.
10. Nagaya N, Kojima M, Uematsu M, Yamagishi M, Hosoda H, Oya H, Hayashi Y, Kangawa K. Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. Am J Physiol 2001;280:R1483—7.
11. Horvath TL, Diano S, Sotonyi P, Heiman M, Tschop M. Minireview: ghrelin and the regulation of energy balance — a hypothalamic perspective. Endocrinology 2001;142:4163—9.
12. Mano-Otagiri A, Nemoto T, Sekino A, et al. Growth hormone-releasing hormone (GHRH) neurons in the arcuate nucleus (Arc) of the hypothalamus are decreased in transgenic rats whose expression of ghrelin receptor is attenuated: evidence that ghrelin receptor is involved in the up-regulation of GHRH expression in the arc. Endocrinology. 2006;147(9):4093–4103.
13. Olszewski PK, Li D, Grace MK, Billington CJ, Kotz CM, Levine AS. Neural basis of orexigenic effects of ghrelin acting within lateral hypothalamus. Peptides. 2003;24(4):597–602.
14. Z. B. Andrews, Z.-W. Liu, N. Walllingford et al., “UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals,” Nature, 2012; 454, no. 7206: 846–851
15. H. Y. Chen, M. E. Trumbauer, A. S. Chen et al., “Orexigenic action of peripheral ghrelin is mediated by neuropeptide Y and agouti-related protein,” Endocrinology, 2004;145(6): 2607– 2612.
16. L. L. Anderson, S. Jeftinija, and C. G. Scanes, “Growth hormone secretion: molecular and cellular mechanisms and in vivo approaches,” Experimental Biology and Medicine, 2004; 229(4):291–302.
17. Baldanzi G, Filigheddu N, Cutrupi S, Catapano F, Bonissoni S, Fubini A, Malan D, Baj G, Granata R, Broglio F, Papotti M, Surico N, Bussolino F, Isgaard J, Deghenghi R, Sinigaglia F, Prat M, Muccioli G, Ghigo E, Graziani A. Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/ AKT. J Cell Biol,2002; 159: 1029 –1037.
18. Li WG, Gavrila D, Liu X, Wang L, Gunnlaugsson S, Stoll LL, McCormick ML, Sigmund CD, Tang C, Weintraub NL. Ghrelin inhibits proinflammatory responses and nuclear factorkappaB activation in human endothelial cells. Circulation 2004;109:2221—6.
19. Nagaya N, Uematsu M, Kojima M, Ikeda Y, Yoshihara F, Shimizu W, Hosoda H, Hirota Y, Ishida H, Mori H, Kangawa K. Chronic administration of ghrelin improves left ventricular dysfunction and attenuates development of cardiac cachexia in rats with heart failure. Circulation 2001;104:1430—5.
20. Matsumura K, Tsuchihashi T, Fujii K, Abe I, Iida M. Central ghrelin modulates sympathetic activity in conscious rabbits. Hypertension 2002;40:694—9.
21. Lin Y, Matsumura K, Fukuhara M, Kagiyama S, Fujii K, Iida M. Ghrelin acts at the nucleus of the solitary tract to decrease arterial pressure in rats. Hypertension 2004;43:977—82.
22. Okumura H, Nagaya N, Enomoto M, Nakagawa E, Oya H, Kangawa K. Vasodilatory effect of ghrelin, an endogenous peptide from the stomach. J Cardiovasc Pharmacol 2002;39:779—83.
23. Baldanzi G, Filigheddu N, Cutrupi S, Catapano F, Bonissoni S, Fubini A, Malan D, Baj G, Granata R, Broglio F, Papotti M, Surico N, Bussolino F, Isgaard J, Deghenghi R, et al. Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT. J Cell Biol 2002;159:1029—37.
24. Nguyen, D.H., and Taub, D. 2002. Cholesterol is essential for macrophage inflammatory protein 1 beta binding and conformational integrity of CC chemokine receptor 5. Blood. 99:4298–4306.
25. Schwenke D O, Tokudome T, Kishimoto I et al. Early Ghrelin treatment after myocardial infarction prevents an increase in cardiac sympathetic tone and reduces mortality. Endocrinology 2008;149(10):5172-5176.
26. Nagaya N, Miyatake K, Uematsu M, Oya H, Shimizu W, Hosoda H, et al. Hemodynamic, renal, and hormonal effects of ghrelin infusion in patients with chronic heart failure. J Clin Endocrinol Metab 2001; 86: 5854–9.
27. Li WG, Gavrila D, Liu X, Wang L, Gunnlaugsson S, Stoll LL, et al. Ghrelin inhibits proinflammatory responses and nuclear factor-kappaB activation in human endothelial cells. Circulation 2004;109: 2221–6.
28. Imanishi R, Ashizawa N, Ohtsuru A, Seto S, Akiyama-Uchida Y, Kawano H, et al. GH suppresses TGF-beta-mediated fibrosis and retains cardiac diastolic function. Mol Cell Endocrinol 2004;218: 137–46.
29. Baldanzi G, Filigheddu N, Cutrupi S, Catapano F, Bonissoni S, Fubini A, Malan D, Baj G, Granata R, Broglio F, Papotti M, Surico N, Bussolino F, Isgaard J, Deghenghi R, Sinigaglia F, Prat M, Muccioli G, Ghigo E, Graziani A. Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/ AKT. J Cell Biol,2002; 159: 1029 –1037.
30. Soeki T, Kishimoto I, Schwenke D O et al. Ghrelin suppresses cardiac sympathetic activity and prevents early left ventricular remodeling in rats with myocardial infarction. Am J Physiol Heart Circ Physiol, 2008; 294: H426–H432.
31. Chang L, Ren Y, Liu X, Li WG, Yang J, Geng B, Weintraub NL, Tang C. Protective effects of ghrelin on ischemia/reperfusion injury in the isolated rat heart. J Cardiovasc Pharmacol,2004; 43: 165–170.
32. Conti E, Andreotti F, Sciahbasi A, Riccardi P, Marra G, Menini E, Ghirlanda G, Maseri A. Markedly reduced insulin-like growth factor-1 in the acute phase of myocardial infarction. J Am Coll Cardiol,2001; 38: 26 –32.
33. Sutton MG, Sharpe N. Left ventricular remodeling after myocardial infarction: pathophysiology and therapy. Circulation, 2000; 101: 2981–2988.
34. Nishiue T, Tsuji H, Tarumi N, Tokunaga S, Tamura K, Masaki M, Inada M, Iwasaka T. Heart rate variability and left ventricular dilatation early after myocardial infarction. J Electrocardiol, 1999; 32: 263–268.
35. Iglesias MJ, Pineiro R, Blanco M, Gallego R, Dieguez C, Gualillo O, Gonzalez-Juanatey JR, Lago F. Growth hormone releasing peptide (ghrelin) is synthesized and secreted by cardiomyocytes. Cardiovasc Res, 2004; 62: 481– 488.
36. Verhulst PJ, Janssen S, Tack J, Depoortere I. Role of the AMP-activated protein kinase (AMPK) signaling pathway in the orexigenic effects of endogenous ghrelin. Regulatory Peptides. 2012;173(1–3):27–35.
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