Aliases APLN, APEL, XNPEP2, apelin
External IDs OMIM: 300297 MGI: 1353624 HomoloGene: 8498 GeneCards: APLN
Species Human Mouse









RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr X: 129.65 – 129.65 Mb Chr X: 48.03 – 48.03 Mb
PubMed search [1] [2]
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Apelin (also known as APLN) is a peptide that in humans is encoded by the APLN gene.[3] Apelin is the endogenous ligand for the G-protein-coupled APJ receptor[4][5][6][7][8] that is expressed at the surface of some cell types.[9] It is widely expressed in various organs such as the heart, lung, kidney, liver, adipose tissue, gastrointestinal tract, brain, adrenal glands, endothelium, and human plasma.


Apelin is a new peptide that was identified in 1998 by Professor M. Fujino’s team.[3]


Apelin gene encodes a pre-proprotein of 77 amino acids,[3] with a signal peptide in the N-terminal region. After translocation into the endoplasmic reticulum and cleavage of the signal peptide, the proprotein of 55 amino acids may generate several active fragments: a 36 amino acid peptide corresponding to the sequence 42-77 (apelin 36), a 17 amino acid peptide corresponding to the sequence 61-77 (apelin 17) and a 13 amino acid peptide corresponding to the sequence 65-77 (apelin 13). This latter fragment may also undergo a pyroglutamylation at the level of its N-terminal glutamine residue. However the presence and/or the concentrations of those peptides in human plasma has been questioned.[10] Recently, 46 different apelin peptides ranging from apelin 55 (proapelin) to apelin 12 have been identified in bovine colostrum, including C-ter truncated isoforms.[11]

Physiological functions

The sites of receptor expression are clearly linked to the different functions played by apelin in the organism.


Vascular expression of the receptor[12][13] participates in the control of blood pressure[4] and its activation promotes the formation of new blood vessels (angiogenesis).[13][14][15][16] The hypotensive effect of apelin results from the activation of receptors expressed at the surface of endothelial cells.[12][13] This activation induces the release of NO,[17] a potent vasodilator, which induces relaxation of the smooth muscle cells of artery wall. Studies performed on mice knocked out for the apelin receptor gene[18] have suggested the existence of a balance between angiotensin II signalling, which increases blood pressure and apelin signalling, which lowers blood pressure. The angiogenic activity is the consequence of apelin action on the proliferation and migration of the endothelial cells. Apelin activates inside the cell transduction cascades (ERKs, Akt, and p70S6kinase phosphorylation),[14][19] which lead to the proliferation of endothelial cells and the formation of new blood vessels[15] It is interesting that knockout of apelin gene is associated with a delay in the development of the retinal vasculature.[20]


The apelin receptor is expressed early during the embryonic development of the heart, where it regulates the migration of cell progenitors fated to differentiate into cardiomyocytes, the contractile cells of the heart.[21][22] Its expression is also detected in the cardiomyocytes of the adult where apelin behaves as one of the most potent stimulator of cardiac contractility.[5][23][24] Aged apelin knockout mice develop progressive impairment of cardiac contractility.[25] Apelin acts as a mediator of the cardiovascular control, including for blood pressure and blood flow. It is one of the most potent stimulators of cardiac contractility yet identified, and plays a role in cardiac tissue remodeling. Apelin levels are increased in left ventricles of patients with chronic heart failure and also in patients with chronic liver disease.[26]


Apelin receptor is also expressed in the neurons of brain areas involved in regulating water and food intake.[4][27][28] Apelin injection increases water intake[4] and apelin decreases the hypothalamic secretion of the antidiuretic hormone vasopressin.[29] This diuretic effect of apelin in association with its hypotensive effect participates in the homeostatic regulation of body fluid. Apelin is also detected in brain areas which control appetite, but its effects on food intake are very contradictory.[30][31][32]

Adipose tissue

Apelin is expressed and secreted by adipocytes, and its production is increased during adipocyte differentiation and is stimulated by insulin.[33] Most obese people have elevated levels of insulin, which may therefore be the reason why obese people have been reported to also have elevated levels of apelin.[33]


Apelin receptor is expressed in several cell types of the gastro-intestinal tract : stomach enterochromaffine-like cells;[34][35] unknown cells of endocrine pancreas,[36] colon epithelial cells.[37] In stomach, activation of receptors on enterochromaffine-like cells by apelin secreted by parietal cells can inhibit histamine release by enterochromaffine-like cells, which in turn decreases acid secretion by parietal cells.[35] In pancreas, apelin inhibits the insulin secretion induced by glucose.[38] This inhibition reveals the functional interdependency between apelin signalling and insulin signalling observed at the adipocyte level where insulin stimulate apelin production.[33] Recently, receptor expression was also detected in skeletic muscle cells. Its activation is involved in glucose uptake and participates in the control of glucose blood levels glycemia.[39]


Receptor expression is also observed at the surface of osteoblasts, the cell progenitors involved in bone formation.[40]


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  2. "Mouse PubMed Reference:".
  3. 1 2 3 Tatemoto K, Hosoya M, Habata Y, Fujii R, Kakegawa T, Zou MX, Kawamata Y, Fukusumi S, Hinuma S, Kitada C, Kurokawa T, Onda H, Fujino M (1998). "Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor". Biochem. Biophys. Res. Commun. 251 (2): 471–6. doi:10.1006/bbrc.1998.9489. PMID 9792798.
  4. 1 2 3 4 Lee DK, Cheng R, Nguyen T, Fan T, Kariyawasam AP, Liu Y, Osmond DH, George SR, O'Dowd BF (2000). "Characterization of apelin, the ligand for the APJ receptor". J. Neurochem. 74 (1): 34–41. doi:10.1046/j.1471-4159.2000.0740034.x. PMID 10617103.
  5. 1 2 Szokodi I, Tavi P, Földes G, Voutilainen-Myllylä S, Ilves M, Tokola H, Pikkarainen S, Piuhola J, Rysä J, Tóth M, Ruskoaho H (2002). "Apelin, the novel endogenous ligand of the orphan receptor APJ, regulates cardiac contractility". Circ. Res. 91 (5): 434–40. doi:10.1161/01.RES.0000033522.37861.69. PMID 12215493.
  6. Kleinz MJ, Davenport AP (2005). "Emerging roles of apelin in biology and medicine". Pharmacol. Ther. 107 (2): 198–211. doi:10.1016/j.pharmthera.2005.04.001. PMID 15907343.
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  18. Ishida J, Hashimoto T, Hashimoto Y, Nishiwaki S, Iguchi T, Harada S, Sugaya T, Matsuzaki H, Yamamoto R, Shiota N, Okunishi H, Kihara M, Umemura S, Sugiyama F, Yagami K, Kasuya Y, Mochizuki N, Fukamizu A (June 2004). "Regulatory roles for APJ, a seven-transmembrane receptor related to angiotensin-type 1 receptor in blood pressure in vivo". J. Biol. Chem. 279 (25): 26274–9. doi:10.1074/jbc.M404149200. PMID 15087458.
  19. Masri B, Lahlou H, Mazarguil H, Knibiehler B, Audigier Y (January 2002). "Apelin (65-77) activates extracellular signal-regulated kinases via a PTX-sensitive G protein". Biochem. Biophys. Res. Commun. 290 (1): 539–45. doi:10.1006/bbrc.2001.6230. PMID 11779205.
  20. Kasai A, Shintani N, Kato H, Matsuda S, Gomi F, Haba R, Hashimoto H, Kakuda M, Tano Y, Baba A (October 2008). "Retardation of retinal vascular development in apelin-deficient mice". Arterioscler. Thromb. Vasc. Biol. 28 (10): 1717–22. doi:10.1161/ATVBAHA.108.163402. PMID 18599802.
  21. Scott IC, Masri B, D'Amico LA, Jin SW, Jungblut B, Wehman AM, Baier H, Audigier Y, Stainier DY (March 2007). "The g protein-coupled receptor agtrl1b regulates early development of myocardial progenitors". Dev. Cell. 12 (3): 403–13. doi:10.1016/j.devcel.2007.01.012. PMID 17336906.
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  40. Xie H, Tang SY, Cui RR, Huang J, Ren XH, Yuan LQ, Lu Y, Yang M, Zhou HD, Wu XP, Luo XH, Liao EY (May 2006). "Apelin and its receptor are expressed in human osteoblasts". Regul. Pept. 134 (2–3): 118–25. doi:10.1016/j.regpep.2006.02.004. PMID 16563531.

Further reading

  • Lee DK, George SR, O'Dowd BF (2006). "Unravelling the roles of the apelin system: prospective therapeutic applications in heart failure and obesity". Trends Pharmacol. Sci. 27 (4): 190–4. doi:10.1016/j.tips.2006.02.006. PMID 16530855. 
  • Lee DK, Saldivia VR, Nguyen T, Cheng R, George SR, O'Dowd BF (2005). "Modification of the terminal residue of apelin-13 antagonizes its hypotensive action". Endocrinology. 146 (1): 231–6. doi:10.1210/en.2004-0359. PMID 15486224. 
  • Lee DK, Lança AJ, Cheng R, Nguyen T, Ji XD, Gobeil F, Chemtob S, George SR, O'Dowd BF (2004). "Agonist-independent nuclear localization of the Apelin, angiotensin AT1, and bradykinin B2 receptors". J. Biol. Chem. 279 (9): 7901–8. doi:10.1074/jbc.M306377200. PMID 14645236. 
  • O'Dowd BF, Heiber M, Chan A, Heng HH, Tsui LC, Kennedy JL, Shi X, Petronis A, George SR, Nguyen T (1993). "A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11". Gene. 136 (1–2): 355–60. doi:10.1016/0378-1119(93)90495-O. PMID 8294032. 
  • Chun HJ, Ali ZA, Kojima Y, Kundu RK, Sheikh AY, Agrawal R, Zheng L, Leeper NJ, Pearl NE, Patterson AJ, Anderson JP, Tsao PS, Lenardo MJ, Ashley EA, Quertermous T (October 2008). "Apelin signaling antagonizes Ang II effects in mouse models of atherosclerosis". The Journal of Clinical Investigation. 118 (10): 3343–54. doi:10.1172/JCI34871. PMC 2525695Freely accessible. PMID 18769630. 
  • Barnes G, Japp AG, Newby DE (July 2010). "Translational promise of the apelin--APJ system". Heart. 96 (13): 1011–6. doi:10.1136/hrt.2009.191122. PMID 20584856. 

External links

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