REVIEW PAPER
Apelin-12 and its receptor as diagnostic biomarkers of childhood and adult diseases
 
More details
Hide details
 
Publication date: 2018-03-19
 
 
Pediatr Pol 2018;93(1):66-73
 
KEYWORDS
ABSTRACT
White adipose tissue is a dynamic endocrine organ able to produce and release several bioactive adipokines, among them apelin, known as the ligand of the G-protein-coupled receptor APJ. The apelin/APJ system, distributed in diverse periphery organ tissues, is mainly involved in insulin sensitivity, food intake, and in the pathomechanism of childhood obesity. It regulates cardiovascular development and function, blood pressure, cardiac contractility, angiogenesis glyco- and fat metabolism and cell proliferation, apoptosis, and inflammation. Apelin inhibits water intake and vasopressin production. Apelin is mainly expressed in the endothelium, vascular smooth muscle cells, brain, heart, lung, testis, ovary, liver, placental tissue, mammary gland, and breast milk. This hormone is a key player in haemostasis with an ability to inhibit thrombin- and collagen-mediated platelet activation. The hepatic apelin/APJ system is markedly activated in progression of biliary atresia, especially in end-stage cirrhosis. In chronic heart failure plasma apelin concentrations are decreased and in patients with hypothyroidism are abnormally high. Apelin is a potential diagnostic marker for differentiating moyamoya disease and intracranial atherosclerosis and a novel biomarker for predicting type 2 diabetes in men. Children with primary hypertension show higher apelin concentration than healthy children. Apelin is implicated in the pathogenesis of childhood atopic asthma. In infants large for gestational age hiperapelinemia is noted. Apelin may function as a mitogenic agent for osteoblasts, may be involved in the development of diabetic nephropathy, retinal neovascularisation of retinopathy of prematurity, and have a diagnostic value in neonatal sepsis.
REFERENCES (76)
1.
Siemińska L. Tkanka tłuszczowa. Patofizjologia, rozmieszczenie, różnice płciowe oraz znaczenie w procesach zapalnych i nowotworowych. Endokrynol Pol 2007; 58: 330-342.
 
2.
Woźniak SE, Gee LI, Wachtel MS, Frezza EE. Adipose tissue: the new endocrine organ? A review article. Dig Dis Sci 2009; 54: 1847-1856.
 
3.
Jacobi D, Stanya KJ, Lee CH. Adipose tissue signaling by nuclear receptors in metabolic complications of obesity. Adipocyte 2012; 1: 4-12.
 
4.
Nedergaard J, Petrovic N, Lingren EM i wsp. PPARgamma in the control of brown adipocyte differentiation. Biochem Biophys Acta 2005; 1740: 293-304.
 
5.
Kilroy GE, Foster SJ, Wu X i wsp. Cytokine profile of human adipose-derived cells: expression of angiogenic, hematopoietic and pro-inflammatory factors. J Cell Physiol 2007; 212: 702-709.
 
6.
Zhang Y, Proenca R, Maffei M i wsp. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372: 425-432.
 
7.
Leal V de O, Mafra D. Adipokines in obesity. Clin Chim Acta 2013; 419: 87-94.
 
8.
Briana DD, Boutsikou M, Boutsikou T, Malamitsi-Puchner A. Associations of novel adipocytokines with bone biomarkers in intrauterine growth-restricted fetuses/neonates at term. J Matern Fetal Neonatal Med 2014; 27: 984-988.
 
9.
Cekmez F, Pirgon O, Aydemir G i wsp. Correlation between cord blood apelin and IGF-1 levels in retinopathy of prematurity. Biomar Med 2012; 6: 821-825.
 
10.
Bury A, Kulik-Rechberger B, Migielska-Wołyniec M. Zależność między stężeniem leptyny a płcią, sposobem urodzenia i masą ciała noworodków w pierwszych dniach życia. Endokrynol Ped 2011; 3: 29-36.
 
11.
Hellgren G, Engström E, Smith LE i wsp. Effect of preterm birth on postnatal alipoprotein and adipocytokine profiles. Neonatology 2015; 108: 16-22.
 
12.
Farias DR, Poston L, Franco-Sena AB i wsp. Maternal lipids and leptin concentrations are associated with large-for gestational age birth: a prospective study. Sci Rep 2017; 7: 804.
 
13.
Lazo-de-la-Vega-Monroy ML, Gonzalez-Domingez MI, Zaina S i wsp. Leptin and its receptors in human placenta of small, adequate and large for gestational age newborns. Horm Metab Res 2017; 49: 350-358.
 
14.
Gad GI, Ismail RI, El-Masry SA, Gouda HR. Serum apelin in early-onset neonatal sepsis: it is diagnostic. J Neonatal Perinatal Med 2014; 7: 207-212.
 
15.
Sadownik B, Lukas W, Behrendt J i wsp. An analysis of factors determining serum leptin concentrations in healthy and infected newborns. Neuroendocrinol Lett 2010; 31: 221-228.
 
16.
Stojewska M, Wnęko-Masłoń B, Nawrat A i wsp. Stężenie rezystyny w surowicy noworodków donoszonych, z zakażeniami wewnątrzmacicznymi. Pediatr Pol 2016; 91: 325-331.
 
17.
Wiśniewska-Ulfik D, Godula-Stuglik U, Szymańska A i wsp. Stężenie waspiny u noworodków donoszonych z ostrą niewydolnością oddechową w przebiegu zakażeń wewnątrzmacicznych. Postępy Neonatologii 2016; 1-2: 68-71.
 
18.
Godula-Stuglik U, Wnęko Masłoń B, Stojewska M i wsp. Stężenie greliny i leptyny u noworodków donoszonych, z zakażeniem wewnątrzmacicznym. Postępy Neonatologii 2015; 2: 18-22.
 
19.
Tatemoto K, Hosoya M, Habata Y i wsp. Isolation and characterization of novel endogenous peptide ligand for the human APJ receptor. Biochim Biophys Res Commun 1998; 251: 471-476.
 
20.
Kumar P, Ashokan A, Aradhyam GK. Apelin binding to human APJ receptor leads to biased signaling. Biochim Biophys Acta 2016; 1864: 1748-1756.
 
21.
Kagiyama S, Fukuhara M, Matsumura K i wsp. Central and peripheral cardiovascular actions of apelin in conscious rats. Regul Pep 2005; 125: 55-59.
 
22.
Tatemoto K, Takayama K, Zou MX i wsp. The novel peptide apelin lowers blood pressure via a nitric-oxide-dependent mechanism. Regul Pept 2001; 99: 87-92.
 
23.
Lee DK, Saldivia VR, Nguyen T i wsp. Modification of the terminal residue of apelin-13 antagonizes its hypotensive action. Endocrinology 2005; 146: 231-236.
 
24.
Kalea AZ, Battle D. Apelin and ACE2 in cardiovascular disease. Curr Opin Invest Drugs 2010; 11: 273-282.
 
25.
Tycińska AM, Lisowska A, Musiał WJ, Sobkowicz B. Apelin acute myocardial infarction and heart failure induced by ischemia. Clin Chim Acta 2012; 413: 406-410.
 
26.
Ladeiras-Lopez R, Ferreira-Martins J, Leite-Moreira AF. The apelinergic system: the role played in human physiology and pathology and potential therapeutic applications. Arq Bras Cardiol 2008; 90: 343-349.
 
27.
Wang G, Anini Y, Wei W i wsp. Apelin: a new enteric peptide, localization in the gastrointestinal tract, ontogeny and stimulation of gastric cell proliferation and of cholecystokinin secretion. Endocrinology 2004; 145: 1342-1348.
 
28.
Badillo-Suarez PA, Rodriguez-Cruz M, Nieves-Morales X. Impact of metabolic hormones secreted in human breast milk on nutritional programming in childhood obesity. J Mammary Gland Biol Neoplasia 2017; 22: 171-191.
 
29.
Hwangbo C, Wu J, Papangeli I i wsp. Endothelial APLNR regulates tissue fatty acid uptake and is essential for apelin’s glucose-lowering effects. Sci Trans Med 2017; 9. pii: eaad4000. doi: 10.1126/scitranslmed.aad4000.
 
30.
Hu L, Deeney JT, Nolan CJ i wsp. Regulation of lipolytic activity by long-chain acyl-coenzyme A in islets and adipocytes. Am J Physiol Endocrinol Metab 2005; 289: 1085-1092.
 
31.
Boucher J, Masri B, Daviaud D i wsp. Apelin, a newly identified adipokine up-regulated by insulin and obesity. Endocrinology 2005; 146: 1764-1771.
 
32.
Eyries M, Siegfried G, Ciumas M i wsp. Hypoxia-induced apelin expression regulates endothelial cell proliferation and regenerative angiogenesis. Circ Res 2008; 103: 432-440.
 
33.
Sorli SC, Le Gonidec S, Knibiehler B, Audigier Y. Apelin is a potent activator of tumor neoangiogenesis. Oncogene 2007; 26: 7692-7699.
 
34.
Glassford AJ, Yue P, Sheikh AY i wsp. HIF-1 regulates hypoxia- and insulin-induced expression of apelin in adipocytes. Am J Physiol Endocrinol Metab 2007; 293: E1590- E1596.
 
35.
Yeu P, Jin H, Aillaud M i wsp. Apelin is necessary for the maintenance of insulin sensivity. Am J Physiol Endocrinol Metab 2010; 298: 59-67.
 
36.
Chen H, Liu C, Cheng C i wsp. Effects of apelin peptides on diabetic complications. Curr Protein Pept Sci 2018; 19: 179-189.
 
37.
Gourdy P, Cazals L, Thalamas C i wsp. Apelin administration improves insulin sensivity in overweight men during hyperinsulinaemic-euglycaemic clamp. Diabetes Obes Metab 2018; 20: 157-164.
 
38.
Heinonen MV, Purhonen AK, Miettinen P i wsp. Apelin, orexin-A and leptin plasma levels in morbid obesity and effect of gastric banding. Regul Pep 2005; 130: 7-13.
 
39.
Ba HJ, Chen HS, Su Z i wsp. Association between serum apelin-12 levels and obesity-related markers in Chinese children. PLoS One 2014; 9: e86577.
 
40.
Castan-Laurell I, Vitkova M, Daviaud D i wsp. Effects of hypocaloric diet-induced weight loss in obese women on plasma apelin and adipose tissue expression of apelin and APJ. Eur J Endocrinol 2008; 158: 905-910.
 
41.
Reinehr T, Woelfle J, Roth CL. Lack of association between apelin, insulin resistance, cardiovascular risk factors and obesity in children: a longitudinal analysis. Metabolism 2011; 60: 1349-1354.
 
42.
Higuchi K, Masaki TE, Gotoh K i wsp. Apelin, an APJ receptor ligand, regulated body adiposity and favors the messenger ribonucleic acid expression of uncoupling proteins in mice. Endocrinology 2007; 148: 2690-2697.
 
43.
Hashimoto T, Kihara M, Imai N i wsp. Requirement of apelin receptor system for oxidative stress-linked atherosclerosis. Am J Pathol 2007; 171: 1705-1717.
 
44.
Cekmez F, Canpolat FE, Pirgon O i wsp. Apelin, vaspin, visfatin and adiponectin in large for gestational age infants with insulin resistance. Cytokine 2011; 56: 387-391.
 
45.
Jędzura A, Adamczyk P, Bianid O i wsp. Non-dipping status and selected adipokines concentration in children with primary hypertension. Clin Exp Hypertens 2017; 21: 1-8.
 
46.
Ma WY, Yu TY, Wei JN i wsp. Plasma apelin: a novel biomarker for predicting diabetes. Clin Chim Acta 2014; 435: 18-23.
 
47.
Kotanidou EP, Kalinderi K, Kyrgios J i wsp. Apelin and G212 A apelin receptor gene polymorphism in obese and diabese youth. Pediatr Obes 2015; 10: 213-219.
 
48.
Folino A, Montarolo PG, Samaja M, Rastaldo R. Effects of apelin on the vascular system. Heart Fail Rev 2015; 20: 505-518.
 
49.
Chong KS, Gardner RS, Morton JJ i wsp. Plasma concentrations of the novel peptide apelin are decreased in patients with chronic heart failure. Eur J Heart Fail 2006; 8: 355-360.
 
50.
Lakomkin SV, Tereshchenko SN, Sychev AV i wsp. Biomarkers in heart failure: apelin levels is not assotiated with presence and severity of the disease. Kardiologija 2015; 55: 37-41.
 
51.
Pisarenko OI, Shulzhenko VS, Pelogeykina YA, Studneva IM. Enhancement of crystalloid cardioplegic protection by structural analogs of apelin-12. J Surg Res 2015; 194: 18-24.
 
52.
Folino A, Accomasso L, Giachino C i wsp. Apelin-induced cardioprotection against ischemia/reperfusion injury: roles of epidermal growth factor and Src. Acta Physiol (Oxf) 2017. doi: 10.1111/alpha. 12924.
 
53.
Walker S, Danton MH, Lang AD, Lyall F. Apelin receptor (APJ) expression during cardiopulmonary bypass in children undergoing surgical repair. PLoS One 2014; 9: e 106262.
 
54.
Busch R, Strohbach A, Pennewitz M i wsp. Regulation of the endothelial apelin/APJ system by hemodynamic fluid flow. Cell Signal 2015; 27: 1286-1296.
 
55.
Flahault A, Couvinneau P, Alvear-Perez R i wsp. Role of the vasopressin/apelin balance and potential use of metabolically stable apelin analogs in water metabolism disorders. Front Endocrinol (Lausanne) 2007; 8: 120.
 
56.
Huang Z, Wu L, Chen L. Apelin/APJ system: a novel potential therapy target for kidney disease. J Cell Physiol 2018; 233: 3892-3900.
 
57.
Simsek Y, Celik O, Yilmaz E i wsp. Serum levels of apelin, salusin- alpha and salusin-beta in normal pregnancy and preeclampsia.
 
58.
J Matern Fetal Neonatal Med 2012; 25: 1705-1708.
 
59.
Reaux-le Goazigo A, Alvear-Perez Z, Zizzari P i wsp. Cellular localization of apelin and its receptor in the anterior pituitary: evidence for a direct stimulatory action of apelin on ACTH release. Am J Physiol Endocrinol Metab 2007; 292: 7-15.
 
60.
Cavallaro G, Filippi L, Bagnoli P i wsp. The pathophysiology of retinopathy of prematurity: an update of previous and recent knowledge. Acta Ophthalmol 2014; 92: 2-20.
 
61.
Sunter D, Hewson AK, Dickson SL. Intracerebroventricular injection of apelin-13 reduces food intake in the rat. Neurosci Lett 2003; 15: 1-4.
 
62.
Novakova V, Sandhu GS, Dragoni-Daescu D, Klabusay M. Apelinergic system in endothelial cells and its role in angiogenesis in myocardial ischemia. Vascul Pharmacol 2016; 76: 1-10.
 
63.
Malamitsi-Puchner A, Gourgiotis D, Boutsikou M i wsp. Circulating apelin concentrations in mother/infant pair at term. Acta Pediatr 2007; 96: 1751-1754.
 
64.
Kojima Y, Kundu RK, Cox CM i wsp. Upregulation of the apelin-APJ pathway promotes neointima formation in the carotid ligation model in mouse. Cardiovasc Res 2010; 87: 156-165.
 
65.
Kasai A, Ishimaru Y, Kinjo T i wsp. Apelin is a crucial factor for hypoxia-induced retinal angiogenesis. Arterioscl Thromb Vasc Biol 2010; 30: 2182-2187.
 
66.
Zhang Y, Jiang YR, Lu Q i wsp. Apelin in epiretinal fibrovascular membranes of patiets with rethinopathy of prematurity and the changes after intravitreal bevacizumab. Retina 2013; 33: 613-620.
 
67.
Hu W, Jiang W, Ye L i wsp. Prospective evaluation of the diagnostic value of plasma apelin – 12 for differentiating patients with moyamoya and intracranial atherosclerosis diseases. Sci Rep 2017; 7: 5452.
 
68.
Cayabyab M, Hinuma S, Farzan M i wsp. Apelin, the natural ligand of the orphan seven transmembrane receptor APJ, inhibits human immunodeficiency virus type 1 entry. J Virol 2000; 74: 11972-11976.
 
69.
Visser YP, Walther FJ, Laghmani el H i wsp. Apelin attenuates hyperoxic lung and heart injury in neonatal rats. Am J Respir Crit Care Med 2010; 182: 1239-1250.
 
70.
Adam F, Khatib AM, Lopez JJ i wsp. Apelin: an antithrombotic factor that inhibits platelet function. Blood 2016; 127: 908-920.
 
71.
Soliman M, Arafah M. Apelin protect against multiple organ injury following hemorrhagic shock and decrease the inflammatory response. Int Apol Basic Med Res 2015; 5: 195-199.
 
72.
Gürel A, Doğantekin A, Özkan Y, Aydin S. Serum apelin levels in patients with thyroid dysfunction. Int J Clin Exp Med 2015; 8: 16394-16398.
 
73.
Lewczuk J. Nadciśnienie płucne w śródmiąższowych chorobach płuc. Pneumonol Alergol Pol 2007; 75: 153-157.
 
74.
Machura E, Ziora K, Ziora D i wsp. Serum apelin-12 level is elevated in schoolchildren with atopic astma. Respire Med 2013; 107: 196-201.
 
75.
Lim Yl, Choi E, Jang YO i wsp. Clinical implications of the serum apelin level on portal hypertension and prognosis of liver cirrhosis. Gut Liver 2016; 10: 109-116.
 
76.
Wattanacharaga L, Lu WD, Kundu RK i wsp. Increased bone mass in mice lacking the adipokine apelin. Endocrinology 2013; 154: 2069-2080.
 
Journals System - logo
Scroll to top