Apelin-APJ signaling: A potential therapeutic target for pulmonary arterial hypertension

Molecules and Cells

Volumn 37, Issue 3, 2014, Pages 196-201

  Kim, Jongmin ^a  

^a Sookmyung Women's University   (South Korea)

Author keywords

Apelin APJ pathway; Endothelial cell microRNA; Proliferation; Pulmonary arterial hypertension

Indexed keywords

APELIN; APELIN RECEPTOR; BONE MORPHOGENETIC PROTEIN RECEPTOR 2; ANTIHYPERTENSIVE AGENT; APLN PROTEIN, HUMAN; APLNR PROTEIN, HUMAN; G PROTEIN COUPLED RECEPTOR; SIGNAL PEPTIDE;

CARDIOVASCULAR FUNCTION; CELLULAR DISTRIBUTION; HUMAN; HYPOXIA; NEOPLASM; NONHUMAN; PATHOGENESIS; PROTEIN ANALYSIS; PROTEIN LOCALIZATION; PROTEIN TARGETING; PULMONARY HYPERTENSION; REGULATORY MECHANISM; SHORT SURVEY; SIGNAL TRANSDUCTION; TISSUE DISTRIBUTION; VASCULAR BIOLOGY; ANIMAL; HYPERTENSION, PULMONARY; METABOLISM; MOLECULARLY TARGETED THERAPY; PATHOPHYSIOLOGY; PHYSIOLOGY; PULMONARY ARTERY;

ANIMALS; ANTIHYPERTENSIVE AGENTS; HUMANS; HYPERTENSION, PULMONARY; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; MOLECULAR TARGETED THERAPY; PULMONARY ARTERY; RECEPTORS, G-PROTEIN-COUPLED; SIGNAL TRANSDUCTION;

EID: 84901401598     PISSN: 10168478     EISSN: 02191032     Source Type: Journal    
DOI: 10.14348/molcells.2014.2308     Document Type: Short Survey

References (60)

1. Alastalo, T.P., Li, M., Perez Vde, J., Pham, D., Sawada, H., Wang, J.K., Koskenvuo, M., Wang, L., Freeman, B.A., Chang, H.Y., et al. (2011). Disruption of PPARγ/β-catenin-mediated regulation of apelin impairs BMP-induced mouse and human pulmonary arterial EC survival. J. Clin. Invest. 121, 3735-3746.
2. Ashley, E.A., Powers, J., Chen, M., Kundu, R., Finsterbach, T., Caffarelli, A., Deng, A., Eichhorn, J., Mahajan, R., Agrawal, R., et al. (2005). The endogenous peptide apelin potently improves cardiac contractility and reduces cardiac loading in vivo. Cardiovasc. Res. 65, 73-82.
3. Barst, R.J. (2005). PDGF signaling in pulmonary arterial hypertension. J. Clin. Invest. 115, 2691-2694.
4. Benisty, J.I., McLaughlin, V.V., Landzberg, M.J., Rich, J.D., Newburger, J.W., Rich, S., and Folkman, J. (2004). Elevated basic fibroblast growth factor levels in patients with pulmonary arterial hypertension. Chest 126, 1255-1261.
5. Brock, M., Samillan, V.J., Trenkmann, M., Schwarzwald, C., Ulrich, S., Gay, R.E., Gassmann, M., Ostergaard, L., Gay, S., Speich, R., et al. (2012). AntagomiR directed against miR-20a restores functional BMPR2 signalling and prevents vascular remodelling in hypoxia-induced pulmonary hypertension. Eur. Heart J. doi: 10.1093/eurheartj/ehs060.
6. Budhiraja, R., Tuder, R.M., and Hassoun, P.M. (2004). Endothelial dysfunction in pulmonary hypertension. Circulation 109, 159-165.
7. Chandra, S.M., Razavi, H., Kim, J., Agrawal, R., Kundu, R.K., de Jesus Perez, V., Zamanian, R.T., Quertermous, T., and Chun, H.J. (2011). Disruption of the apelin-APJ system worsens hypoxia-induced pulmonary hypertension. Arterioscler. Thromb. Vasc. Biol. 31, 814-820.
8. Chen, M.M., Ashley, E.A., Deng, D.X., Tsalenko, A., Deng, A., Tabibiazar, R., Ben-Dor, A., Fenster, B., Yang, E., King, J.Y., et al. (2003). Novel role for the potent endogenous inotrope apelin in human cardiac dysfunction. Circulation 108, 1432-1439.
9. Cheng, X., Cheng, X.S., and Pang, C.C. (2003). Venous dilator effect of apelin, an endogenous peptide ligand for the orphan APJ receptor, in conscious rats. Eur. J. Pharmacol. 470, 171-175.
10. Chun, H.J., Ali, Z.A., Kojima, Y., Kundu, R.K., Sheikh, A.Y., Agrawal, R., Zheng, L., Leeper, N.J., Pearl, N.E., Patterson, A.J., et al. (2008). Apelin signaling antagonizes Ang II effects in mouse models of atherosclerosis. J. Clin. Invest. 118, 3343-3354.
11. De Mota, N., Reaux-Le Goazigo, A., El Messari, S., Chartrel, N., Roesch, D., Dujardin, C., Kordon, C., Vaudry, H., Moos, F., and Llorens-Cortes, C. (2004). Apelin, a potent diuretic neuropeptide counteracting vasopressin actions through inhibition of vasopressin neuron activity and vasopressin release. Proc. Natl. Acad. Sci. USA 101, 10464-10469.
12. Deng, Z., Morse, J.H., Slager, S.L., Cuervo, N., Moore, K.J., Venetos, G., Kalachikov, S., Cayanis, E., Fischer, S.G., Barst, R.J., et al. (2000). Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene. Am. J. Hum. Genet. 67, 737-744.
13. Falcão-Pires, I., Gonçalves, N., Henriques-Coelho, T., Moreira-Gonçalves, D., Roncon-Albuquerque, R. Jr., and Leite-Moreira, A.F. (2009). Apelin decreases myocardial injury and improves right ventricular function in monocrotaline-induced pulmonary hypertension. Am. J. Physiol. Heart Circ. Physiol. 296, H2007-H2014.
14. Ghofrani, H.A., Morrell, N.W., Hoeper, M.M., Olschewski, H., Peacock, A.J., Barst, R.J., Shapiro, S., Golpon, H., Toshner, M., Grimminger, F., et al. (2010). Imatinib in pulmonary arterial hypertension patients with inadequate response to established therapy. Am. J. Respir. Crit. Care Med. 182, 1171-1177.
15. Giaid, A., and Saleh, D. (1995). Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension. N. Engl. J. Med. 333, 214-221.
16. Goetze, J.P., Rehfeld, J.F., Carlsen, J., Videbaek, R., Andersen, C. B., Boesgaard, S., and Friis-Hansen, L. (2006). Apelin: a new plasma marker of cardiopulmonary disease. Regul. Pept. 133, 134-138.
17. Hamid, R., Cogan, J.D., Hedges, L.K., Austin, E., Phillips, J.A. 3rd, Newman, J.H., and Loyd, J.E. (2009). Penetrance of pulmonary arterial hypertension is modulated by the expression of normal BMPR2 allele. Hum. Mutat. 30, 649-654.
18. Hanahan, D., and Weinberg, R.A. (2000). The hallmarks of cancer. Cell 100, 57-70.
19. Hansmann, G., Wagner, R.A., Schellong, S., Perez, V.A., Urashima, T., Wang, L., Sheikh, A.Y., Suen, R.S., Stewart, D.J., and Rabinovitch, M. (2007). Pulmonary arterial hypertension is linked to insulin resistance and reversed by peroxisome proliferator-activated receptor-gamma activation. Circulation 115, 1275-1284.
20. Hosoya, M., Kawamata, Y., Fukusumi, S., Fujii, R., Habata, Y., Hinuma, S., Kitada, C., Honda, S., Kurokawa, T., Onda, H., et al. (2000). Molecular and functional characteristics of APJ. Tissue distribution of mRNA and interaction with the endogenous ligand apelin. J. Biol. Chem. 275, 21061-21067.
21. Humbert, M., Sitbon, O., Chaouat, A., Bertocchi, M., Habib, G., Gressin, V., Yaïci, A., Weitzenblum, E., Cordier, J.F., Chabot, F., et al. (2010). Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation 122, 156-163.
22. Ishida, J., Hashimoto, T., Hashimoto, Y., Nishiwaki, S., Iguchi, T., Harada, S., Sugaya, T., Matsuzaki, H., Yamamoto, R., Shiota, N., et al. (2004). Regulatory roles for APJ, a seven-transmembrane receptor related to angiotensin-type 1 receptor in blood pressure in vivo. J. Biol. Chem. 279, 26274-26279.
23. Iwanaga, Y., Kihara, Y., Takenaka, H., and Kita, T. (2006). Downregulation of cardiac apelin system in hypertrophied and failing hearts: Possible role of angiotensin II-angiotensin type 1 receptor system. J. Mol. Cell Cardiol. 41, 798-806.
24. Izikki, M., Guignabert, C., Fadel, E., Humbert, M., Tu, L., Zadigue, P., Dartevelle, P., Simonneau, G., Adnot, S., Maitre, B., et al. (2009). Endothelial-derived FGF2 contributes to the progression of pulmonary hypertension in humans and rodents. J. Clin. Invest. 119, 512-523.
25. Kaneko, F.T., Arroliga, A.C., Dweik, R.A., Comhair, S.A., Laskowski, D., Oppedisano, R., Thomassen, M.J., and Erzurum, S.C. (1998). Biochemical reaction products of nitric oxide as quantitative markers of primary pulmonary hypertension. Am. J. Respir. Crit. Care Med. 158, 917-923.
26. Kang, Y., Kim, J., Anderson, J.P., Wu, J., Gleim, S.R., Kundu, R.K., McLean, D.L., Kim, J.D., Park, H., Jin, S.W., et al. (2013). Apelin-APJ signaling is a critical regulator of endothelial MEF2 activation in cardiovascular development. Circ. Res. 113, 22-31.
27. Kawamata, Y., Habata, Y., Fukusumi, S., Hosoya, M., Fujii, R., Hinuma, S., Nishizawa, N., Kitada, C., Onda, H., Nishimura, O., et al. (2001). Molecular properties of apelin: tissue distribution and receptor binding. Biochim. Biophys. Acta 1538, 162-171.
28. Kim, V.N. (2005). Small RNAs: classification, biogenesis, and function. Mol. Cells 19, 1-15.
29. Kim, Y., and Kim, V.N. (2012). MicroRNA factory: RISC assembly from precursor microRNAs. Mol. Cell 46, 384-386.
30. Kim, J., Kang, Y., Kojima, Y., Lighthouse, J.K., Hu, X., Aldred, M.A., McLean, D.L., Park, H., Comhair, S.A., Greif, D.M., et al. (2013). An endothelial apelin-FGF link mediated by miR-424 and miR-503 is disrupted in pulmonary arterial hypertension. Nat. Med. 19, 74-82.
31. Lee, D.K., Cheng, R., Nguyen, T., Fan, T., Kariyawasam, A.P., Liu, Y., Osmond, D.H., George, S.R., and O'Dowd, B.F. (2000). Characterization of apelin, the ligand for the APJ receptor. J. Neurochem. 74, 34-41.
32. Lin, Z., Kumar, A., SenBanerjee, S., Staniszewski, K., Parmar, K., Vaughan, D.E., Gimbrone, M.A. Jr., Balasubramanian, V., García- Cardeña, G., and Jain, M.K. (2005). Kruppel-like factor 2 (KLF2) regulates endothelial thrombotic function. Circ. Res. 96, e48-e57.
33. Machado, R.D., Eickelberg, O., Elliott, C.G., Geraci, M.W., Hanaoka, M., Loyd, J.E., Newman, J.H., Phillips, J.A. 3rd., Soubrier, F., Trembath, R.C., et al. (2009). Genetics and genomics of pulmonary arterial hypertension. J. Am. Coll. Cardiol. 54, S32-S42.
34. Masri, F.A., Xu, W., Comhair, S.A., Asosingh, K., Koo, M., Vasanji, A., Drazba, J., Anand-Apte, B., and Erzurum, S.C. (2007). Hyperproliferative apoptosis-resistant endothelial cells in idiopathic pulmonary arterial hypertension. Am. J. Physiol. Lung Cell Mol. Physiol. 293, L548-L554.
35. McLaughlin, V.V., and McGoon, M.D. (2006). Pulmonary arterial hypertension. Circulation 114, 1417-1431.
36. McLean, D.L., Kim, J., Kang, Y., Shi, H., Atkins, G.B., Jain, M.K., and Chun, H.J. (2012). Apelin/APJ signaling is a critical regulator of statin effects in vascular endothelial cells. Arterioscler. Thromb. Vasc. Biol. 32, 2640-2643.
37. Medhurst, A.D., Jennings, C.A., Robbins, M.J., Davis, R.P., Ellis, C., Winborn, K.Y., Lawrie, K.W., Hervieu, G., Riley, G., Bolaky, J.E., et al. (2003). Pharmacological and immunohistochemical characterization of the APJ receptor and its endogenous ligand apelin. J. Neurochem. 84, 1162-1172.
38. Moncada, S., and Higgs, E.A. (2006). The discovery of nitric oxide and its role in vascular biology. Br. J. Pharmacol. 147 Suppl 1, S193-S201.
39. O'Carroll, A.M., Lolait, S.J., and Howell, G.M. (2006). Transcriptional regulation of the rat apelin receptor gene: promoter cloning and identification of an Sp1 site necessary for promoter activity. J. Mol. Endocrinol. 36, 221-235.
40. O'Dowd, B.F., Heiber, M., Chan, A., Heng, H.H., Tsui, L.C., Kennedy, J.L., Shi, X., Petronis, A., George, S.R., and Nguyen, T. (1993). A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11. Gene 136, 355-360.
41. Ozkan, M., Dweik, R.A., Laskowski, D., Arroliga, A.C., and Erzurum, S.C. (2001). High levels of nitric oxide in individuals with pulmonary hypertension receiving epoprostenol therapy. Lung 179, 233-243.
42. Parikh, V.N., Jin, R.C., Rabello, S., Gulbahce, N., White, K., Hale, A., Cottrill, K.A., Shaik, R.S., Waxman, A.B., Zhang, Y.Y., et al. (2012). MicroRNA-21 integrates pathogenic signaling to control pulmonary hypertension: results of a network bioinformatics approach. Circulation 125, 1520-1532.
43. Pullamsetti, S.S., Doebele, C., Fischer, A., Savai, R., Kojonazarov, B., Dahal, B.K., Ghofrani, H.A., Weissmann, N., Grimminger, F., Bonauer, A., et al. (2012). Inhibition of microRNA-17 improves lung and heart function in experimental pulmonary hypertension. Am. J. Respir. Crit. Care Med. 185, 409-419.
44. Rabinovitch, M. (2007). Pathobiology of pulmonary hypertension. Annu. Rev. Pathol. 2, 369-399.
45. Rai, P.R., Cool, C.D., King, J.A., Stevens, T., Burns, N., Winn, R.A., Kasper, M., and Voelkel, N.F. (2008). The cancer paradigm of severe pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. 178, 558-564.
46. Raja, S.G. (2010). Endothelin receptor antagonists for pulmonary arterial hypertension: an overview. Cardiovasc. Ther. 28, e65-e71.
47. Roberts, K.E., McElroy, J.J., Wong, W.P., Yen, E., Widlitz, A., Barst, R.J., Knowles, J.A., and Morse, J.H. (2004). BMPR2 mutations in pulmonary arterial hypertension with congenital heart disease. Eur. Respir. J. 24, 371-374.
48. Rubin, L.J. (1997). Primary pulmonary hypertension. N. Engl. J. Med. 336, 111-117.
49. Sakao, S., Tatsumi, K., and Voelkel, N.F. (2010). Reversible or irreversible remodeling in pulmonary arterial hypertension. Am. J. Respir. Cell Mol. Biol. 43, 629-634.
50. Sen-Banerjee, S., Mir, S., Lin, Z., Hamik, A., Atkins, G.B., Das, H., Banerjee, P., Kumar, A., and Jain, M.K. (2005). Kruppel-like factor 2 as a novel mediator of statin effects in endothelial cells. Circulation 112, 720-726.
51. Sheikh, A.Y., Chun, H.J., Glassford, A.J., Kundu, R.K., Kutschka, I., Ardigo, D., Hendry, S.L., Wagner, R.A., Chen, M.M., Ali, Z.A., et al. (2008). In vivo genetic profiling and cellular localization of apelin reveals a hypoxia-sensitive, endothelial-centered pathway activated in ischemic heart failure. Am. J. Physiol. Heart Circ. Physiol. 294, H88-H98.
52. Simonneau, G., Robbins, I.M., Beghetti, M., Channick, R.N., Delcroix, M., Denton, C.P., Elliott, C.G., Gaine, S.P., Gladwin, M.T., Jing, Z.C., et al. (2009). Updated clinical classification of pulmonary hypertension. J. Am. Coll. Cardiol. 54, S43-S54.
53. Szokodi, I., Tavi, P., Földes, G., Voutilainen-Myllylä, S., Ilves, M., Tokola, H., Pikkarainen, S., Piuhola, J., Rysä, J., Tóth, M., et al. (2002). Apelin, the novel endogenous ligand of the orphan receptor APJ, regulates cardiac contractility. Circ. Res. 91, 434-440.
54. Tatemoto, K., Hosoya, M., Habata, Y., Fujii, R., Kakegawa, T., Zou, M.X., Kawamata, Y., Fukusumi, S., Hinuma, S., Kitada, C., et al. (1998). Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochem. Biophys. Res. Commun. 251, 471-476.
55. Tatemoto, K., Takayama, K., Zou, M.X., Kumaki, I., Zhang, W., Kumano, K., and Fujimiya, M. (2001). The novel peptide apelin lowers blood pressure via a nitric oxide-dependent mechanism. Regul. Pept. 99, 87-92.
56. Tuder, R.M., Groves, B., Badesch, D.B., and Voelkel, N.F. (1994). Exuberant endothelial cell growth and elements of inflammation are present in plexiform lesions of pulmonary hypertension. Am. J. Pathol. 144, 275-285.
57. Tuder, R.M., Cool, C.D., Yeager, M., Taraseviciene-Stewart, L., Bull, T.M., and Voelkel, N.F. (2001). The pathobiology of pulmonary hypertension. Endothelium Clin. Chest Med. 22, 405-418.
58. Urbich, C., Kuehbacher, A., and Dimmeler, S. (2008). Role of microRNAs in vascular diseases, inflammation, and angiogenesis. Cardiovasc. Res. 79, 581-588.
59. Zaidi, S.H., You, X.M., Ciura, S., Husain, M., and Rabinovitch, M. (2002). Overexpression of the serine elastase inhibitor elafin protects transgenic mice from hypoxic pulmonary hypertension. Circulation 105, 516-521.
60. Zamanian, R.T., Hansmann, G., Snook, S., Lilienfeld, D., Rappaport, K.M., Reaven, G.M., Rabinovitch, M., and Doyle, R.L. (2009). Insulin resistance in pulmonary arterial hypertension. Eur. Respir. J. 33, 318-324.