Ghrelin as a promising biological marker in cardiovascular disease
- 作者: Alieva A.1, Pinchuk T.1, Baikova I.1, Shnakhova L.2, Voronkova K.1, Valiev R.3, Rakhaev A.4, Arakelyan R.1, Kalova M.1, Nikitin I.1
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隶属关系:
- Pirogov Russian National Research Medical University
- I.M. Sechenov First Moscow State Medical University
- A.S. Loginov Moscow Clinical Scientific and Practical Center
- Kh.M. Berbekov Kabardino-Balkarian State University
- 期: 卷 27, 编号 6 (2021)
- 页面: 589-600
- 栏目: Reviews
- URL: https://journals.rcsi.science/0869-2106/article/view/108896
- DOI: https://doi.org/10.17816/0869-2106-2021-27-6-589-600
- ID: 108896
如何引用文章
详细
This review highlights the current literature data on the peptide hormone ghrelin. Ghrelin is a 28-amino-acid peptide, which is the only known peptide hormone modified with fatty acids. Ghrelin is a natural receptor ligand that stimulates the secretion of growth hormones. In addition to the stomach, ghrelin is expressed in many organs such as the duodenum, jejunum, ileum, colon, lungs, heart, pancreas, kidneys, testicles, pituitary gland, and hypothalamus. The main biological functions of this peptide include growth hormone secretion, appetite stimulation, modulation of gastric acid secretion and motility, and an increase in endocrine and exocrine pancreatic secretions. Reference intervals for ghrelin are 8.502–16.6 pg/mL. The studies analyzed have shown a strong relationship between ghrelin and cardiovascular system function. Studies have also described the cardioprotective effects of ghrelin. However, the molecular mechanisms underlying the effects of ghrelin on the heart are not fully understood. A further deeper understanding of the role of ghrelin and future clinical studies are necessary to determine the diagnostic, prognostic, and possibly therapeutic significance of this biomarker.
作者简介
Amina Alieva
Pirogov Russian National Research Medical University
编辑信件的主要联系方式.
Email: amisha_alieva@mail.ru
ORCID iD: 0000-0001-5416-8579
SPIN 代码: 2749-6427
MD, Cand. Sci. (Med.), assistant professor
俄罗斯联邦, 1, Ostrovityanova st., Moscow, 117997Tatyana Pinchuk
Pirogov Russian National Research Medical University
Email: doktor2000@inbox.ru
ORCID iD: 0000-0002-7877-4407
MD, Cand. Sci. (Med.), assistant professor
俄罗斯联邦, 1, Ostrovityanova st., Moscow, 117997Irina Baikova
Pirogov Russian National Research Medical University
Email: 1498553@mail.ru
ORCID iD: 0000-0003-0886-6290
SPIN 代码: 3054-8884
MD, Cand. Sci. (Med.), assistant professor
俄罗斯联邦, 1, Ostrovityanova st., Moscow, 117997Lidia Shnakhova
I.M. Sechenov First Moscow State Medical University
Email: Shnakhova_I_m@staff.sechenov.ru
ORCID iD: 0000-0003-3000-0987
俄罗斯联邦, Moscow
Kira Voronkova
Pirogov Russian National Research Medical University
Email: kiravoronkova@yandex.ru
ORCID iD: 0000-0003-1111-6378
SPIN 代码: 1636-7627
MD, Dr. Sci. (Med.), professor
俄罗斯联邦, 1, Ostrovityanova st., Moscow, 117997Ramiz Valiev
A.S. Loginov Moscow Clinical Scientific and Practical Center
Email: Radiosurgery@bk.ru
ORCID iD: 0000-0003-1613-3716
SPIN 代码: 2855-2867
MD, Cand. Sci. (Med.)
俄罗斯联邦, MoscowAlik Rakhaev
Kh.M. Berbekov Kabardino-Balkarian State University
Email: alikrahaev@yandex.ru
ORCID iD: 0000-0001-9601-1174
MD, Dr. Sci. (Med.), professor
俄罗斯联邦, NalchikRoza Arakelyan
Pirogov Russian National Research Medical University
Email: Elmira.sharm@yandex.ru
俄罗斯联邦, 1, Ostrovityanova st., Moscow, 117997
Marina Kalova
Pirogov Russian National Research Medical University
Email: marina717717@mail.ru
ORCID iD: 0000-0002-8949-4523
俄罗斯联邦, 1, Ostrovityanova st., Moscow, 117997
Igor Nikitin
Pirogov Russian National Research Medical University
Email: igor.nikitin.64@mail.ru
ORCID iD: 0000-0003-1699-0881
MD, Dr. Sci. (Med.), professor
俄罗斯联邦, 1, Ostrovityanova st., Moscow, 117997参考
- Kojima M, Hosoda H, Date Y, et al. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999;402(6762):656–660. doi: 10.1038/45230
- Tokudome T, Otani K, Miyazato M, Kangawa K. Ghrelin and the heart. Peptides. 2019;111:42–46. doi: 10.1016/j.peptides.2018.05.006
- Howard AD, Feighner SD, Cully DF, et al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science. 1996;273(5277):974–977. doi: 10.1126/science.273.5277.974
- Tokudome T, Kangawa K. Physiological significance of ghrelin in the cardiovascular system. Proc Jpn Acad Ser B Phys Biol Sci. 2019;95(8):459–467. doi: 10.2183/pjab.95.032
- Zhang JV, Ren PG, Avsian-Kretchmer O, et al. Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake. Science. 2005;310(5750):996–999. doi: 10.1126/science.1117255
- Kim S, Nam Y, Shin SJ, et al. The Potential Roles of Ghrelin in Metabolic Syndrome and Secondary Symptoms of Alzheimer’s Disease. Front Neurosci. 2020;14:583097. doi: 10.3389/fnins.2020.583097
- Nunez-Salces M, Li H, Feinle-Bisset C, et al. The regulation of gastric ghrelin secretion. Acta Physiol (Oxf). 2021;231(3):e13588. doi: 10.1111/apha.13588
- Bang AS, Soule SG, Yandle TG, et al. Characterisation of proghrelin peptides in mammalian tissue and plasma. J Endocrinol. 2007;192(2):313–323. doi: 10.1677/JOE-06-0021
- Hosoda H, Kojima M, Matsuo H, Kangawa K. Purification and characterization of rat des-Gln14-Ghrelin, a second endogenous ligand for the growth hormone secretagogue receptor. J Biol Chem. 2000;275(29):21995–22000. doi: 10.1074/jbc.M002784200
- Hopkins AL, Nelson TA, Guschina IA, et al. Unacylated ghrelin promotes adipogenesis in rodent bone marrow via ghrelin O-acyl transferase and GHS-R1a activity: evidence for target cell-induced acylation. Sci Rep. 2017;7:45541. doi: 10.1038/srep45541
- Yanagi S, Sato T, Kangawa K, Nakazato M. The Homeostatic Force of Ghrelin. Cell Metab. 2018;27(4):786–804. doi: 10.1016/j.cmet.2018.02.008
- Tauber M, Coupaye M, Diene G, et al. Prader-Willi syndrome: A model for understanding the ghrelin system. J Neuroendocrinol. 2019;31(7):e12728. doi: 10.1111/jne.12728
- Lv Y, Liang T, Wang G, Li Z. Ghrelin, a gastrointestinal hormone, regulates energy balance and lipid metabolism. Biosci Rep. 2018;38(5). doi: 10.1042/BSR20181061
- Sakata I, Takemi S. Ghrelin-cell physiology and role in the gastrointestinal tract. Curr Opin Endocrinol Diabetes Obes. 2021;28(2):238–242. doi: 10.1097/MED.0000000000000610
- Date Y, Kojima M, Hosoda H, et al. Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology. 2000;141(11):4255–4261. doi: 10.1210/endo.141.11.7757
- Tichonenko EV, Tsoi UA, Vasilieva EY, Babenko AY. Characteristics of eating behavior and the level of hormones regulating the appetite in patients with type 2 diabetes mellitus and body mass index more than 35 kg /m2. Obesity and metabolism. 2018;15(1):30–38. (In Russ). doi: 10.14341/omet2018130-38
- Lewinski A, Karbownik-Lewinska M, Wieczorek-Szukala K, et al. Contribution of Ghrelin to the Pathogenesis of Growth Hormone Deficiency. Int J Mol Sci. 2021;22(16). doi: 10.3390/ijms22169066
- Airapetov MI, Eresko SO, Lebedev AA, et al. [Expression of Ghrelin Receptor GHS-R1a in The Brain (Mini Review)]. Mol Biol (Mosk). 2021;55(4):578–584. doi: 10.31857/S0026898421040029
- Xiao X, Bi M, Jiao Q, et al. A new understanding of GHSR1a –independent of ghrelin activation. Ageing Res Rev. 2020;64:101187. doi: 10.1016/j.arr.2020.101187
- Gnanapavan S, Kola B, Bustin SA, et al. The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab. 2002;87(6):2988. doi: 10.1210/jcem.87.6.8739
- Gupta S, Mitra A. Heal the heart through gut (hormone) ghrelin: a potential player to combat heart failure. Heart Fail Rev. 2021;26(2):417–435. doi: 10.1007/s10741-020-10032-2
- Belik EV, Gruzdeva OV, Dyleva YA, et al. Diagnosis of insulin resistance in patients at high cardiovascular risk: focus on peptide hormone ghrelin. Ateroscleroz. 2019;15(3):42–49. (In Russ). doi: 10.15372/ATER20190303
- Matsumura K, Tsuchihashi T, Fujii K, et al. Central ghrelin modulates sympathetic activity in conscious rabbits. Hypertension. 2002;40(5):694–699. doi: 10.1161/01.hyp.0000035395.51441.10
- Mao Y, Tokudome T, Otani K, et al. Excessive sympathoactivation and deteriorated heart function after myocardial infarction in male ghrelin knockout mice. Endocrinology. 2013;154(5):1854–1863. doi: 10.1210/en.2012-2132
- Mager U, Kolehmainen M, Lindstrom J, et al. Association between ghrelin gene variations and blood pressure in subjects with impaired glucose tolerance. Am J Hypertens. 2006;19(9):920–926. doi: 10.1016/j.amjhyper.2006.02.017
- Sato T, Nakashima Y, Nakamura Y, et al. Continuous antagonism of the ghrelin receptor results in early induction of salt-sensitive hypertension. J Mol Neurosci. 2011;43(2):193–199. doi: 10.1007/s12031-010-9414-1
- Yu AP, Ugwu FN, Tam BT, et al. Ghrelin Axis Reveals the Interacting Influence of Central Obesity and Hypertension. Front Endocrinol (Lausanne). 2018;9:534. doi: 10.3389/fendo.2018.00534
- Zhang M, Fang WY, Qu XK, et al. AMPK activity is down-regulated in endothelial cells of GHS-R(-/-) mice. Int J Clin Exp Pathol. 2013;6(9):1770–1780. PMC3759483
- Virdis A, Duranti E, Colucci R, et al. Ghrelin restores nitric oxide availability in resistance circulation of essential hypertensive patients: role of NAD(P)H oxidase. Eur Heart J. 2015;36(43):3023–3030. doi: 10.1093/eurheartj/ehv365
- Yang D, Liu Z, Zhang H, Luo Q. Ghrelin protects human pulmonary artery endothelial cells against hypoxia-induced injury via PI3-kinase/Akt. Peptides. 2013;42:112–117. doi: 10.1016/j.peptides.2013.01.012
- Yuan MJ, Li W, Zhong P. Research progress of ghrelin on cardiovascular disease. Biosci Rep. 2021;41(1). doi: 10.1042/BSR20203387
- Mao Y, Tokudome T, Otani K, et al. Ghrelin prevents incidence of malignant arrhythmia after acute myocardial infarction through vagal afferent nerves. Endocrinology. 2012;153(7):3426–3434. doi: 10.1210/en.2012–1065
- Ma T, Su Y, Lu S, et al. Ghrelin expression and significance in 92 patients with atrial fibrillation. Anatol J Cardiol. 2017;18(2):99–102. doi: 10.14744/AnatolJCardiol.2017.7621
- Sax B, Merkely B, Turi K, et al. Characterization of pericardial and plasma ghrelin levels in patients with ischemic and non-ischemic heart disease. Regul Pept. 2013;186:131–136. doi: 10.1016/j.regpep.2013.08.003
- Akboga MK, Tacoy G, Yilmaz Demirtas C, et al. As cardioprotective and angiogenic biomarker, can ghrelin predict coronary collateral development and severity of coronary atherosclerosis? Turk Kardiyol Dern Ars. 2017;45(4):316-323. doi: 10.5543/tkda.2017.96169
- Pearson JT, Collie N, Lamberts RR, et al. Ghrelin Preserves Ischemia-Induced Vasodilation of Male Rat Coronary Vessels Following beta-Adrenergic Receptor Blockade. Endocrinology. 2018;159(4):1763–1773. doi: 10.1210/en.2017-03070
- Gruzdeva OV, Karetnikova VN, Akbasheva OЕ, et al. Lipid, Adipokine аnd Ghrelin Concentrations in Myocardial Infarction Patients with Insulin Resistance. Annals of the Russian Academy of Medical Sciences. 2013;68(7):13–19. (In Russ). doi: 10.15690/vramn.v68i7.706
- Raghay K, Akki R, Bensaid D, Errami M. Ghrelin as an anti-inflammatory and protective agent in ischemia/reperfusion injury. Peptides. 2020;124:170226. doi: 10.1016/j.peptides.2019.170226
- Gao M, Yang J, Liu G, et al. Ghrelin promotes the differentiation of human embryonic stem cells in infarcted cardiac microenvironment. Peptides. 2012;34(2):373–379. doi: 10.1016/j.peptides.2012.02.006
- Matsumoto M, Yasuda S, Miyazaki S, et al. Decreased serum ghrelin levels in patients with acute myocardial infarction. Tohoku J. Exp Med. 2013;231(3):235–242. doi: 10.1620/tjem.231.235
- Sullivan R, McGirr R, Hu S, et al. Changes in the Cardiac GHSR1a-Ghrelin System Correlate With Myocardial Dysfunction in Diabetic Cardiomyopathy in Mice. J Endocr Soc. 2018;2(2):178–189. doi: 10.1210/js.2017-00433
- Yang C, Liu J, Liu K, et al. Ghrelin suppresses cardiac fibrosis of post-myocardial infarction heart failure rats by adjusting the activin A-follistatin imbalance. Peptides. 2018;99:27–35. doi: 10.1016/j.peptides.2017.10.018
- Wang M, Qian L, Li J, et al. GHSR deficiency exacerbates cardiac fibrosis: role in macrophage inflammasome activation and myofibroblast differentiation. Cardiovasc Res. 2020;116(13):2091–2102. doi: 10.1093/cvr/cvz318
- Eid RA, Alkhateeb MA, Eleawa S, et al. Cardioprotective effect of ghrelin against myocardial infarction-induced left ventricular injury via inhibition of SOCS3 and activation of JAK2/STAT3 signaling. Basic Res Cardiol. 2018;113(2):13. doi: 10.1007/s00395-018-0671-4
- Yuan MJ, Wang T. The new mechanism of Ghrelin/GHSR-1a on autophagy regulation. Peptides. 2020;126:170264. doi: 10.1016/j.peptides.2020.170264
- Sullivan R, Randhawa VK, Stokes A, et al. Dynamics of the Ghrelin/Growth Hormone Secretagogue Receptor System in the Human Heart Before and After Cardiac Transplantation. J Endocr Soc. 2019;3(4):748–762. doi: 10.1210/js.2018-00393
- Aleksova A, Beltrami AP, Bevilacqua E, et al. Ghrelin Derangements in Idiopathic Dilated Cardiomyopathy: Impact of Myocardial Disease Duration and Left Ventricular Ejection Fraction. J Clin Med. 2019;8(8). doi: 10.3390/jcm8081152
- Elhadidy MG, Elmasry A, Rabei MR, Eladel AE. Effect of ghrelin on VEGF-B and connexin-43 in a rat model of doxorubicin-induced cardiomyopathy. J Basic Clin Physiol Pharmacol. 2019;31(1). doi: 10.1515/jbcpp-2018-0212
- Sullivan R, Randhawa VK, Lalonde T, et al. Regional Differences in the Ghrelin-Growth Hormone Secretagogue Receptor Signalling System in Human Heart Disease. CJC Open. 2021;3(2):182–194. doi: 10.1016/j.cjco.2020.10.015
- Yuan Y, Huang F, Deng C, Zhu P. The Additional Prognostic Value of Ghrelin for Mortality and Readmission in Elderly Patients with Acute Heart Failure. Clin Interv Aging. 2020;15:1353–1363. doi: 10.2147/CIA.S259889
- Chen Y, Zhou S, Zhang A, et al. Temporal changes and prognostic value of plasma ghrelin level in patients with acute heart failure: a prospective study. Heart Vessels. 2022;37(3):419–425. doi: 10.1007/s00380-021-01935-7
- Aliyeva AM, Reznik EV, Hasanova ET, et al. Clinical Value of Blood Biomarkers in Patients with Chronic Heart Failure. The Russian Archives of Internal Medicine. 2018;8(5):333–345. (In Russ). doi: 10.20514/2226-6704-2018-8-5-333-345
- Aliyevа AM, Almazova II, Pinchuk TV, et al. The value of copeptin in the diagnosis and prognosis of cardiovascular diseases. Clinical Medicine (Russian Journal). 2020;98(3):203–209. (In Russ). doi: 10.30629/0023-2149-2020-98-3-203-209
- Alieva AM, Almazova II, Pinchuk TV, et al. Fractalkin and cardiovascular disease. Consilium Medicum. 2020;22(5):83–86. (In Russ). doi: 10.26442/20751753.2020.5.200186
- Alieva AM, Pinchuk TV, Batov MA, et al. Sindecan-1 and cardiovascular diseases. Therapy. 2021;(8):121–128. (In Russ). doi: https://dx.doi.org/10.18565/therapy.2021.8.121-128.
- Alieva AM, Pinchuk TV, Almazova II, et al. Сlinical value of blood biomarker ST2 in patients with chronic heart failure. Consilium Medicum. 2021;23(6):522–526. (In Russ). doi: 10.26442/20751753.2021.6.200606
- Aliyeva AM, Baykova IE, Kislyakov VA, et al. Galactin-3: diagnostic and prognostic value in patients with chronic heart failure. Terapevticheskii arkhiv. 2019;91(9):145–149. (In Russ). doi: 10.26442/00403660.2019.09.000226
- Gruzdeva OV, Borodkina DA, Belik EV, et al. Ghrelin Physiology and Pathophysiology: Focus on the Cardiovascular System. Kardiologiia. 2019;59(3):60–67. (In Russ). doi: 10.18087/cardio.2019.3.10220