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

The effects of corticotropin-releasing hormone, also known as corticotropin-releasing factor (CRF), on the cardiovascular system have been intensively researched since its discovery. Moreover, the actions of urocortin (Ucn) I on the cardiovascular system have also been intensively scrutinized following the cloning and identification of its receptor, CRF receptor type 2 (CRFR2), in peripheral tissues including the heart. Given the cardioprotective actions of CRFR2 ligands, the clinical potential of not only Ucn I but also Ucn II and III, which were later identified as more specific ligands for CRFR2, has received considerable attention from researchers. In addition, recent work has indicated that CRF type 1 receptor may be also involved in cardioprotection against ischemic/reperfusion injury. Here we provide a historical overview of research on Ucn I and related agents, their effects on the cardiovascular system, and the clinical potential of the use of such agents to treat cardiovascular diseases.

[1]  N. Chattipakorn,et al.  Plasma urocortin in acute myocardial infarction patients , 2010, European journal of clinical investigation.

[2]  G. Faggian,et al.  Activation of Src protein tyrosine kinase plays an essential role in urocortin-mediated cardioprotection , 2010, Molecular and Cellular Endocrinology.

[3]  K. Peterson,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 , 2010, European journal of heart failure.

[4]  Xiuxia Liu,et al.  Effect of long-term treatment with urocortin on the activity of somatic angiotensin-converting enzyme in spontaneously hypertensive rats. , 2010, Canadian journal of physiology and pharmacology.

[5]  A. Richards,et al.  Urocortin 2 induces potent long-lasting inhibition of cardiac sympathetic drive despite baroreflex activation in conscious sheep. , 2010, The Journal of endocrinology.

[6]  A. Richards,et al.  Urocortin 2 Inhibits Furosemide-Induced Activation of Renin and Enhances Renal Function and Diuretic Responsiveness in Experimental Heart Failure , 2009, Circulation. Heart failure.

[7]  Juejin Wang,et al.  Urocortin induced expression of COX‐2 and ICAM‐1 via corticotrophin‐releasing factor type 2 receptor in rat aortic endothelial cells , 2009, British journal of pharmacology.

[8]  R. Doughty,et al.  Plasma Urocortin 1 in Human Heart Failure , 2009, Circulation. Heart failure.

[9]  Jue Hu,et al.  Urocortin promotes the development of vasculitis in a rat model of thromboangiitis obliterans via corticotrophin‐releasing factor type 1 receptors , 2009, British journal of pharmacology.

[10]  J. Vaughan,et al.  A novel corticotropin‐releasing factor receptor splice variant exhibits dominant negative activity: a putative link to stress‐induced heart disease , 2009, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[11]  D. Mary,et al.  Urocortin II Induces Nitric Oxide Production Through cAMP and Ca2+ Related Pathways in Endothelial Cells , 2009, Cellular Physiology and Biochemistry.

[12]  S. Hazen,et al.  Differential effects of arginine methylation on diastolic dysfunction and disease progression in patients with chronic systolic heart failure. , 2008, European heart journal.

[13]  M. Kurabayashi,et al.  Effect of atrial natriuretic peptide on left ventricular remodelling in patients with acute myocardial infarction. , 2008, European heart journal.

[14]  C. Frampton,et al.  Urocortin 2 infusion in human heart failure. , 2007, European heart journal.

[15]  R. Knight,et al.  Urocortin prevents mitochondrial permeability transition in response to reperfusion injury indirectly by reducing oxidative stress. , 2007, American journal of physiology. Heart and circulatory physiology.

[16]  A. Richards,et al.  Urocortin 1 administration from onset of rapid left ventricular pacing represses progression to overt heart failure. , 2007, American journal of physiology. Heart and circulatory physiology.

[17]  C. Frampton,et al.  Urocortin 2 infusion in healthy humans: hemodynamic, neurohormonal, and renal responses. , 2007, Journal of the American College of Cardiology.

[18]  T. Suda,et al.  Urocortin induces interleukin-6 gene expression via cyclooxygenase-2 activity in aortic smooth muscle cells. , 2006, Endocrinology.

[19]  V. Cameron,et al.  Urocortin 3: haemodynamic, hormonal, and renal effects in experimental heart failure. , 2006, European heart journal.

[20]  A. Richards,et al.  Plasma urocortin 1 in sheep: Regional sampling and effects of experimental heart failure , 2006, Peptides.

[21]  F. Wang,et al.  Effects of intravenous urocortin on angiotensin-converting enzyme in rats. , 2006, Vascular pharmacology.

[22]  K. Hirata,et al.  Endothelial Urocortin Has Potent Antioxidative Properties and Is Upregulated by Inflammatory Cytokines and Pitavastatin , 2006, Journal of Vascular Research.

[23]  V. Cameron,et al.  Integrated Hemodynamic, Hormonal, and Renal Actions of Urocortin 2 in Normal and Paced Sheep: Beneficial Effects in Heart Failure , 2005, Circulation.

[24]  K. Nakao,et al.  Effects of urocortin II on neonatal rat cardiac myocytes and non-myocytes , 2005, Peptides.

[25]  C. Frampton,et al.  Four-day urocortin-I administration has sustained beneficial haemodynamic, hormonal, and renal effects in experimental heart failure. , 2005, European heart journal.

[26]  Shengnan Li,et al.  In vivo protective effects of urocortin on ischemia-reperfusion injury in rat heart via free radical mechanisms. , 2005, Canadian journal of physiology and pharmacology.

[27]  M. Hubank,et al.  Cardioprotection mediated by urocortin is dependent upon PKCε activation , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[28]  M. Saruta,et al.  Expression of urocortin III/stresscopin in human heart and kidney. , 2004, The Journal of clinical endocrinology and metabolism.

[29]  Alon Chen,et al.  Specificity and regulation of extracellularly regulated kinase1/2 phosphorylation through corticotropin-releasing factor (CRF) receptors 1 and 2beta by the CRF/urocortin family of peptides. , 2004, Endocrinology.

[30]  I. Squire,et al.  Plasma urocortin in human systolic heart failure. , 2004, Clinical science.

[31]  Yusu Gu,et al.  The cardiovascular physiologic actions of urocortin II: acute effects in murine heart failure. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[32]  N. Tajima,et al.  Cardiac expression of urocortin (Ucn) in diseased heart; preliminary results on possible involvement of Ucn in pathophysiology of cardiac diseases , 2003, Molecular and Cellular Biochemistry.

[33]  D. Latchman,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. , 2004, Endocrinology.

[34]  T. Benraad,et al.  Hypotensive effects of ovine and human corticotrophin-releasing factors in man , 2004, European Journal of Clinical Pharmacology.

[35]  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. , 2003, Journal of molecular and cellular cardiology.

[36]  T. Suda,et al.  Vasodilative Effects of Urocortin II via Protein Kinase A and a Mitogen-activated Protein Kinase in Rat Thoracic Aorta , 2003, Journal of cardiovascular pharmacology.

[37]  T. Suda,et al.  Urocortin-related peptides increase interleukin-6 output via cyclic adenosine 5'-monophosphate-dependent pathways in A7r5 aortic smooth muscle cells. , 2003, Endocrinology.

[38]  B. Climént,et al.  Relaxation of rat arteries by urocortin: effects of gender and diabetes , 2003, The Journal of pharmacy and pharmacology.

[39]  V. Cameron,et al.  Minireview: natriuretic peptides during development of the fetal heart and circulation. , 2003, Endocrinology.

[40]  C. Frampton,et al.  Beneficial hemodynamic, endocrine, and renal effects of urocortin in experimental heart failure: comparison with normal sheep. , 2002, Journal of the American College of Cardiology.

[41]  K. Nakao,et al.  Urocortin has cell-proliferative effects on cardiac non-myocytes. , 2002, Life sciences.

[42]  R. Raddino,et al.  Urocortin promotes hemodynamic and bioenergetic recovery and improves cell survival in the isolated rat heart exposed to ischemia/reperfusion. , 2002, Journal of the American College of Cardiology.

[43]  L. Monge,et al.  Relaxation by urocortin of human saphenous veins , 2002, British journal of pharmacology.

[44]  R. Knight,et al.  Activation of protein kinase B/Akt by urocortin is essential for its ability to protect cardiac cells against hypoxia/reoxygenation-induced cell death. , 2002, Journal of molecular and cellular cardiology.

[45]  Kazuhiro Takahashi,et al.  Expression of urocortin and corticotropin-releasing factor receptor subtypes in the human heart. , 2002, The Journal of clinical endocrinology and metabolism.

[46]  C. Donaldson,et al.  Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[47]  J. Vaughan,et al.  Urocortin II: A member of the corticotropin-releasing factor (CRF) neuropeptide family that is selectively bound by type 2 CRF receptors , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[48]  T. Horio,et al.  Urocortin, a member of the corticotropin-releasing factor family, in normal and diseased heart. , 2000, American journal of physiology. Heart and circulatory physiology.

[49]  W. Vale,et al.  Regulation of Corticotropin-Releasing Factor Receptor Type 2β Messenger Ribonucleic Acid in the Rat Cardiovascular System by Urocortin, Glucocorticoids, and Cytokines. , 2000, Endocrinology.

[50]  Susan E. Murray,et al.  Abnormal adaptations to stress and impaired cardiovascular function in mice lacking corticotropin-releasing hormone receptor-2 , 2000, Nature Genetics.

[51]  R. Knight,et al.  Urocortin Protects against Ischemic and Reperfusion Injury via a MAPK-dependent Pathway* , 2000, The Journal of Biological Chemistry.

[52]  K. Nakao,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. , 1998, Biochemical and biophysical research communications.

[53]  R. Knight,et al.  Expression and protective effects of urocortin in cardiac myocytes , 1998, Neuropeptides.

[54]  J. Vaughan,et al.  Cardiac inotropic actions of urocortin in conscious sheep. , 1997, The American journal of physiology.

[55]  K. Nakao,et al.  Stimulation by corticotropin-releasing factor of atrial natriuretic peptide and brain natriuretic peptide secretions from cultured neonatal rat cardiomyocytes. , 1996, Biochemical and biophysical research communications.

[56]  David Lovejoy,et al.  Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor , 1995, Nature.

[57]  T. Lovenberg,et al.  CRF2 alpha and CRF2 beta receptor mRNAs are differentially distributed between the rat central nervous system and peripheral tissues. , 1995, Endocrinology.

[58]  R. Cone,et al.  Identification of a novel murine receptor for corticotropin-releasing hormone expressed in the heart. , 1995, Molecular endocrinology.

[59]  C. Donaldson,et al.  Identification of a second corticotropin-releasing factor receptor gene and characterization of a cDNA expressed in heart. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[60]  M. Rosenfeld,et al.  A sauvagine/corticotropin-releasing factor receptor expressed in heart and skeletal muscle. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[61]  T. Lovenberg,et al.  Cloning and characterization of a functionally distinct corticotropin-releasing factor receptor subtype from rat brain. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[62]  A. Grünert,et al.  Effect of corticotropin releasing factor on atrial natriuretic peptide release from the isolated perfused rat heart. , 1994, Arzneimittel-Forschung.

[63]  J. Born,et al.  Effects of corticotropin-releasing factor on isolated rat heart activity. , 1993, The American journal of physiology.

[64]  L. Duntas,et al.  Dilatory and Inotropic Effects of Corticotropin-Releasing Factor (CRF) on the Isolated Heart , 1992, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[65]  齋藤 誠.  Effect of corticotropin-releasing factor on the electrical and mechanical activities of the guinea-pig ventricular myocardium , 1991 .

[66]  J. Hasegawa,et al.  Effect of corticotropin-releasing factor on the electrical and mechanical activities of the guinea-pig ventricular myocardium. , 1990, General pharmacology.

[67]  J. Kiang,et al.  CRF-evoked bradycardia in urethane-anesthetized rats is blocked by naloxone , 1985, Peptides.

[68]  L. Fisher,et al.  Corticotropin-releasing factor (CRF): mechanism to elevate mean arterial pressure and heart rate , 1983, Regulatory Peptides.

[69]  W. Vale,et al.  Corticotropin-releasing factor (CRF): central effects on mean arterial pressure and heart rate in rats. , 1982, Endocrinology.

[70]  W. Vale,et al.  Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. , 1982, Science.

[71]  W. Vale,et al.  Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin , 1981 .