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International Journal of Endocrinology
Volume 2012, Article ID 198628, 5 pages
http://dx.doi.org/10.1155/2012/198628
Review Article

Clinical Perspectives of Urocortin and Related Agents for the Treatment of Cardiovascular Disease

1Department of Molecular Cell Biology, Institute of DNA Medicine, Research Center for Medical Sciences, Jikei University School of Medicine, Tokyo 105-8461, Japan
2Division of Diabetes and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo 105-8461, Japan

Received 21 November 2011; Revised 7 February 2012; Accepted 7 February 2012

Academic Editor: Kazunori Kageyama

Copyright © 2012 Keiichi Ikeda et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. Grunt, J. Glaser, H. Schmidhuber, P. Pauschinger, and J. Born, “Effects of corticotropin-releasing factor on isolated rat heart activity,” American Journal of Physiology, vol. 264, no. 4, pp. H1124–H1129, 1993. View at Google Scholar · View at Scopus
  2. M. Grunt, C. Haug, L. Duntas, P. Pauschinger, V. Maier, and E. F. Pfeiffer, “Dilatory and inotropic effects of corticotropin-releasing factor (CRF) on the isolated heart. Effects on atrial natriuretic peptide (ANP) release,” Hormone and Metabolic Research, vol. 24, no. 2, pp. 56–59, 1992. View at Google Scholar · View at Scopus
  3. L. A. Fisher, J. Rivier, C. Rivier, J. Spiess, W. Vale, and M. R. Brown, “Corticotropin-releasing factor (CRF): central effects on mean arterial pressure and heart rate in rats,” Endocrinology, vol. 110, no. 6, pp. 2222–2224, 1982. View at Google Scholar · View at Scopus
  4. L. A. Fisher, G. Jessen, and M. R. Brown, “Corticotropin-releasing factor (CRF): mechanism to elevate mean arterial pressure and heart rate,” Regulatory Peptides, vol. 5, no. 2, pp. 153–161, 1983. View at Google Scholar · View at Scopus
  5. J. G. Kiang and E. T. Wei, “CRF-evoked bradycardia in urethane-anesthetized rats is blocked by naloxone,” Peptides, vol. 6, no. 3, pp. 409–413, 1985. View at Google Scholar · View at Scopus
  6. W. Vale, J. Spiess, C. Rivier, and J. Rivier, “Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and β-endorphin,” Science, vol. 213, no. 4514, pp. 1394–1397, 1981. View at Google Scholar · View at Scopus
  7. A. R. Hermus, G. F. Pieters, J. J. Willemsen et al., “Hypotensive effects of ovine and human corticotrophin-releasing factors in man,” European Journal of Clinical Pharmacology, vol. 31, no. 5, pp. 531–534, 1987. View at Google Scholar
  8. M. Saitoh, J. Hasegawa, and H. Mashiba, “Effect of corticotropin-releasing factor on the electrical and mechanical activities of the guinea-pig ventricular myocardium,” General Pharmacology, vol. 21, no. 3, pp. 337–342, 1990. View at Publisher · View at Google Scholar · View at Scopus
  9. C. Haug, M. Grunt, S. Schmid et al., “Effect of corticotropin releasing factor on atrial natriuretic peptide release from the isolated perfused rat heart,” Arzneimittel-Forschung, vol. 44, no. 5, pp. 579–582, 1994. View at Google Scholar · View at Scopus
  10. T. W. Lovenberg, D. T. Chalmers, C. Liu, and E. B. De Souza, “CRF2α and CRF2β receptor mRNAs are differentially distributed between the rat central nervous system and peripheral tissues,” Endocrinology, vol. 136, no. 9, pp. 4139–4142, 1995. View at Google Scholar · View at Scopus
  11. T. W. Lovenberg, C. W. Liaw, D. E. Grigoriadis et al., “Cloning and characterization of a functionally distinct corticotropin-releasing factor receptor subtype from rat brain,” Proceedings of the National Academy of Sciences of the United States of America, vol. 92, no. 3, pp. 836–840, 1995. View at Publisher · View at Google Scholar · View at Scopus
  12. P. Stenzel, R. Kesterson, W. Yeung, R. D. Cone, M. B. Rittenberg, and M. P. Stenzel-Poore, “Identification of a novel murine receptor for corticotropin-releasing hormone expressed in the heart,” Molecular Endocrinology, vol. 9, no. 5, pp. 637–645, 1995. View at Google Scholar · View at Scopus
  13. T. Kishimoto, R. V. Pearse II, C. R. Lin, and M. G. Rosenfeld, “A sauvagine/corticotropin-releasing factor receptor expressed in heart and skeletal muscle,” Proceedings of the National Academy of Sciences of the United States of America, vol. 92, no. 4, pp. 1108–1112, 1995. View at Publisher · View at Google Scholar · View at Scopus
  14. M. Perrin, C. Donaldson, R. Chen et al., “Identification of a second corticotropin-releasing factor receptor gene and characterization of a cDNA expressed in heart,” Proceedings of the National Academy of Sciences of the United States of America, vol. 92, no. 7, pp. 2969–2973, 1995. View at Publisher · View at Google Scholar · View at Scopus
  15. J. Vauhan, C. Donaldson, J. Bittencourt et al., “Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor,” Nature, vol. 378, no. 6554, pp. 287–292, 1995. View at Google Scholar · View at Scopus
  16. A. Okosi, B. K. Brar, M. Chan et al., “Expression and protective effects of urocortin in cardiac myocytes,” Neuropeptides, vol. 32, no. 2, pp. 167–171, 1998. View at Publisher · View at Google Scholar · View at Scopus
  17. K. Tojo, S. Sato, G. Tokudome et al., “Stimulation by corticotropin-releasing factor of atrial natriuretic peptide and brain natriuretic peptide secretions from cultured neonatal rat cardiomyocytes,” Biochemical and Biophysical Research Communications, vol. 225, no. 2, pp. 340–346, 1996. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  18. K. Ikeda, K. Tojo, S. Sato et al., “Urocortin, a newly identified corticotropin-releasing factor-related mammalian peptide, stimulates atrial natriuretic peptide and brain natriuretic peptide secretions from neonatal rat cardiomyocytes,” Biochemical and Biophysical Research Communications, vol. 250, no. 2, pp. 298–304, 1998. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  19. V. A. Cameron and L. J. Ellmers, “Minireview: natriuretic peptides during development of the fetal heart and circulation,” Endocrinology, vol. 144, no. 6, pp. 2191–2194, 2003. View at Publisher · View at Google Scholar · View at Scopus
  20. S. Kasama, M. Furuya, T. Toyama, S. Ichikawa, and M. Kurabayashi, “Effect of atrial natriuretic peptide on left ventricular remodelling in patients with acute myocardial infarction,” European Heart Journal, vol. 29, no. 12, pp. 1485–1494, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  21. D. G. Parkes, J. Vaughan, J. Rivier, W. Vale, and C. N. May, “Cardiac inotropic actions of urocortin in conscious sheep,” American Journal of Physiology, vol. 272, no. 5, pp. H2115–H2122, 1997. View at Google Scholar · View at Scopus
  22. T. Nishikimi, A. Miyata, T. Horio et al., “Urocortin, a member of the corticotropin-releasing factor family, in normal and diseased heart,” American Journal of Physiology, vol. 279, no. 6, pp. H3031–H3039, 2000. View at Google Scholar · View at Scopus
  23. K. Ikeda, K. Tojo, Y. Oki, and K. Nakao, “Urocortin has cell-proliferative effects on cardiac non-myocytes,” Life Sciences, vol. 71, no. 16, pp. 1929–1938, 2002. View at Publisher · View at Google Scholar · View at Scopus
  24. B. K. Brar, A. K. Jonassen, A. Stephanou et al., “Urocortin protects against ischemic and reperfusion injury via a MAPK- dependent pathway,” The Journal of Biological Chemistry, vol. 275, no. 12, pp. 8508–8514, 2000. View at Publisher · View at Google Scholar · View at Scopus
  25. T. M. Scarabelli, E. Pasini, A. Stephanou et al., “Urocortin promotes hemodynamic and bioenergetic recovery and improves cell survival in the isolated rat heart exposed to ischemia/reperfusion,” Journal of the American College of Cardiology, vol. 40, no. 1, pp. 155–161, 2002. View at Publisher · View at Google Scholar · View at Scopus
  26. Y. Kimura, K. Takahashi, K. Totsune et al., “Expression of urocortin and corticotropin-releasing factor receptor subtypes in the human heart,” Journal of Clinical Endocrinology and Metabolism, vol. 87, no. 1, pp. 340–346, 2002. View at Publisher · View at Google Scholar · View at Scopus
  27. K. Ikeda, K. Tojo, G. Tokudome et al., “Cardiac expression of urocortin (Ucn) in diseased heart; preliminary results on possible involvement of Ucn in pathophysiology of cardiac diseases,” Molecular and Cellular Biochemistry, vol. 252, no. 1-2, pp. 25–32, 2003. View at Publisher · View at Google Scholar · View at Scopus
  28. C. N. Liu, C. Yang, X. Y. Liu, and S. Li, “In vivo protective effects of urocortin on ischemia-reperfusion injury in rat heart via free radical mechanisms,” Canadian Journal of Physiology and Pharmacology, vol. 83, no. 6, pp. 459–465, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  29. S. Meili-Butz, K. Bühler, D. John et al., “Acute effects of urocortin 2 on cardiac function and propensity for arrhythmias in an animal model of hypertension-induced left ventricular hypertrophy and heart failure,” European Journal of Heart Failure, vol. 12, no. 8, pp. 797–804, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  30. C. J. Charles, D. L. Jardine, M. T. Rademaker, and A. M. Richards, “Urocortin 2 induces potent long-lasting inhibition of cardiac sympathetic drive despite baroreflex activation in conscious sheep,” Journal of Endocrinology, vol. 204, no. 2, pp. 181–189, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  31. S. C. Coste, R. A. Kesterson, K. A. Heldwein et al., “Abnormal adaptations to stress and impaired cardiovascular function in mice lacking corticotropin-releasing hormone receptor-2,” Nature Genetics, vol. 24, no. 4, pp. 403–409, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  32. Y. Sztainberg, Y. Kuperman, O. Issler et al., “A novel corticotropin-releasing factor receptor splice variant exhibits dominant negative activity: a putative link to stress-induced heart disease,” The FASEB Journal, vol. 23, no. 7, pp. 2186–2196, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  33. T. M. Reyes, K. Lewis, M. H. Perrin et al., “Urocortin II: a member of the corticotropin-releasing factor (CRF) neuropeptide family that is selectively bound by type 2 CRF receptors,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 5, pp. 2843–2848, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  34. K. Lewis, C. Li, M. H. Perrin et al., “Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 13, pp. 7570–7575, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  35. K. Ikeda, K. Tojo, C. Otsubo et al., “Effects of urocortin II on neonatal rat cardiac myocytes and non-myocytes,” Peptides, vol. 26, no. 12, pp. 2473–2481, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  36. A. Chanalaris, K. M. Lawrence, A. Stephanou et al., “Protective effects of the urocortin homologues stresscopin (SCP) and stresscopin-related peptide (SRP) against hypoxia/reoxygenation injury in rat neonatal cardiomyocytes,” Journal of Molecular and Cellular Cardiology, vol. 35, no. 10, pp. 1295–1305, 2003. View at Publisher · View at Google Scholar · View at Scopus
  37. K. Takahashi, K. Totsune, O. Murakami et al., “Expression of urocortin III/stresscopin in human heart and kidney,” Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 4, pp. 1897–1903, 2004. View at Publisher · View at Google Scholar · View at Scopus
  38. K. Kageyama, G. E. Gaudriault, M. J. Bradbury, and W. W. Vale, “Regulation of corticotropin-releasing factor receptor type 2β messenger ribonucleic acid in the rat cardiovascular system by urocortin, glucocorticoids, and cytokines,” Endocrinology, vol. 141, no. 7, pp. 2285–2293, 2000. View at Publisher · View at Google Scholar · View at Scopus
  39. T. Honjo, N. Inoue, R. Shiraki et al., “Endothelial urocortin has potent antioxidative properties and is upregulated by inflammatory cytokines and pitavastatin,” Journal of Vascular Research, vol. 43, no. 2, pp. 131–138, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  40. K. Kageyama, K. Furukawa, I. Miki, K. Terui, S. Motomura, and T. Suda, “Vasodilative effects of urocortin II via protein kinase A and a mitogen-activated protein kinase in rat thoracic aorta,” Journal of Cardiovascular Pharmacology, vol. 42, no. 4, pp. 561–565, 2003. View at Publisher · View at Google Scholar · View at Scopus
  41. E. Sanz, N. Fernández, L. Monge, B. Climent, G. Diéguez, and A. L. García-Villalón, “Relaxation of rat arteries by urocortin: effects of gender and diabetes,” Journal of Pharmacy and Pharmacology, vol. 55, no. 6, pp. 783–788, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  42. E. Sanz, L. Monge, N. Fernández et al., “Relaxation by urocortin of human saphenous veins,” British Journal of Pharmacology, vol. 136, no. 1, pp. 90–94, 2002. View at Google Scholar · View at Scopus
  43. Y. Xu, R. Zhang, J. Chen et al., “Urocortin promotes the development of vasculitis in a rat model of thromboangiitis obliterans via corticotrophin-releasing factor type 1 receptors,” British Journal of Pharmacology, vol. 157, no. 8, pp. 1368–1379, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  44. R. Zhang, Y. Xu, H. Fu, J. Wang, L. Jin, and S. Li, “Urocortin induced expression of COX-2 and ICAM-1 via corticotrophin- releasing factor type 2 receptor in rat aortic endothelial cells,” British Journal of Pharmacology, vol. 158, no. 3, pp. 819–829, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  45. Z. Yuan, R. McCauley, C. Chen-Scarabelli et al., “Activation of Src protein tyrosine kinase plays an essential role in urocortin-mediated cardioprotection,” Molecular and Cellular Endocrinology, vol. 325, no. 1-2, pp. 1–7, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  46. K. Kageyama and T. Suda, “Urocortin-related peptides increase interleukin-6 output via cyclic adenosine 5′-monophosphate-dependent pathways in A7r5 aortic smooth muscle cells,” Endocrinology, vol. 144, no. 6, pp. 2234–2241, 2003. View at Publisher · View at Google Scholar · View at Scopus
  47. B. K. Brar, A. Chen, M. H. Perrin, and W. Vale, “Specificity and regulation of extracellularly regulated kinase1/2 phosphorylation through corticotropin-releasing factor (CRF) receptors 1 and 2β by the CRF/urocortin family of peptides,” Endocrinology, vol. 145, no. 4, pp. 1718–1729, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  48. E. Grossini, C. Molinari, D. A. Mary et al., “Urocortin II induces nitric oxide production through cAMP and Ca2+ related pathways in endothelial cells,” Cellular Physiology and Biochemistry, vol. 23, no. 1–3, pp. 87–96, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  49. B. K. Brar, A. Stephanou, R. Knight, and D. Latchman, “Activation of protein kinase B/Akt by urocortin is essential for its ability to protect cardiac cells against hypoxia/reoxygenation-induced cell death,” Journal of Molecular and Cellular Cardiology, vol. 34, no. 4, pp. 483–492, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  50. K. M. Lawrence, A. M. Kabir, M. Bellahcene et al., “Cardioprotection mediated by urocortin is dependent on PKCε activation,” The FASEB Journal, vol. 19, no. 7, pp. 831–833, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  51. P. A. Townsend, S. M. Davidson, S. J. Clarke et al., “Urocortin prevents mitochondrial permeability transition in response to reperfusion injury indirectly by reducing oxidative stress,” American Journal of Physiology, vol. 293, no. 2, pp. H928–H938, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  52. K. Kageyama, K. Hanada, T. Nigawara et al., “Urocortin induces interleukin-6 gene expression via cyclooxygenase-2 activity in aortic smooth muscle cells,” Endocrinology, vol. 147, no. 9, pp. 4454–4462, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  53. B. K. Brar, A. K. Jonassen, E. M. Egorina et al., “Urocortin-II and urocortin-III are cardioprotective against ischemia reperfusion injury: an essential endogenous cardioprotective role for corticotropin releasing factor receptor Type 2 in the murine heart,” Endocrinology, vol. 145, no. 1, pp. 24–35, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  54. L. L. Ng, I. W. Loke, R. J. O'Brien, I. B. Squire, and J. E. Davies, “Plasma urocortin in human systolic heart failure,” Clinical Science, vol. 106, no. 4, pp. 383–388, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  55. W. H. Wilson Tang, W. Tong, K. Shrestha et al., “Differential effects of arginine methylation on diastolic dysfunction and disease progression in patients with chronic systolic heart failure,” European Heart Journal, vol. 29, no. 20, pp. 2506–2513, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  56. A. Phrommintikul, S. Sivasinprasasn, N. Lailerd, S. Chattipakorn, S. Kuanprasert, and N. Chattipakorn, “Plasma urocortin in acute myocardial infarction patients,” European Journal of Clinical Investigation, vol. 40, no. 10, pp. 874–882, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  57. C. J. Charles, M. T. Rademaker, A. M. Richards, and T. G. Yandle, “Plasma urocortin 1 in sheep: regional sampling and effects of experimental heart failure,” Peptides, vol. 27, no. 7, pp. 1801–1805, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  58. S. P. Wright, R. N. Doughty, C. M. Frampton, G. D. Gamble, T. G. Yandle, and A. M. Richards, “Plasma urocortin 1 in human heart failure,” Circulation, vol. 2, no. 5, pp. 465–471, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  59. M. T. Rademaker, C. J. Charles, E. A. Espiner et al., “Beneficial hemodynamic, endocrine, and renal effects of urocortin in experimental heart failure: comparison with normal sheep,” Journal of the American College of Cardiology, vol. 40, no. 8, pp. 1495–1505, 2002. View at Publisher · View at Google Scholar · View at Scopus
  60. T. L. Bale, M. Hoshijima, Y. Gu et al., “The cardiovascular physiologic actions of urocortin II: acute effects in murine heart failure,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 10, pp. 3697–3702, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  61. M. T. Rademaker, C. J. Charles, E. A. Espiner, C. M. Frampton, J. G. Lainchbury, and A. M. Richards, “Four-day urocortin-I administration has sustained beneficial haemodynamic, hormonal, and renal effects in experimental heart failure,” European Heart Journal, vol. 26, no. 19, pp. 2055–2062, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  62. M. T. Rademaker, V. A. Cameron, C. J. Charles, and A. M. Richards, “Integrated hemodynamic, hormonal, and renal actions of urocortin 2 in normal and paced sheep: beneficial effects in heart failure,” Circulation, vol. 112, no. 23, pp. 3624–3632, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  63. M. T. Rademaker, V. A. Cameron, C. J. Charles, and A. M. Richards, “Urocortin 3: haemodynamic, hormonal, and renal effects in experimental heart failure,” European Heart Journal, vol. 27, no. 17, pp. 2088–2098, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  64. M. T. Rademaker, C. J. Charles, and A. M. Richards, “Urocortin 1 administration from onset of rapid left ventricular pacing represses progression to overt heart failure,” American Journal of Physiology, vol. 293, no. 3, pp. H1536–H1544, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  65. M. E. Davis, C. J. Pemberton, T. G. Yandle et al., “Urocortin 2 infusion in human heart failure,” European Heart Journal, vol. 28, no. 21, pp. 2589–2597, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  66. M. T. Rademaker, C. J. Charles, M. G. Nicholls, and A. M. Richards, “Urocortin 2 inhibits furosemide-induced activation of renin and enhances renal function and diuretic responsiveness in experimental heart failure,” Circulation, vol. 2, no. 6, pp. 532–540, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  67. C. Yang, Y. Xu, T. Mendez, F. Wang, Q. Yang, and S. Li, “Effects of intravenous urocortin on angiotensin-converting enzyme in rats,” Vascular Pharmacology, vol. 44, no. 4, pp. 238–246, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  68. C. Yang, X. Liu, and S. Li, “Effect of long-term treatment with urocortin on the activity of somatic angiotensin-converting enzyme in spontaneously hypertensive rats,” Canadian Journal of Physiology and Pharmacology, vol. 88, no. 2, pp. 168–176, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  69. M. E. Davis, C. J. Pemberton, T. G. Yandle et al., “Urocortin 2 infusion in healthy humans. hemodynamic, neurohormonal, and renal responses,” Journal of the American College of Cardiology, vol. 49, no. 4, pp. 461–471, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus