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.

• Publication year

  2012

• Venue

  International Journal of Endocrinology

• Publication date

  2012-04-03

• Fields of study

  Medicine

• Identifiers
  DOI 10.1155/2012/198628PMID 22548056PMCID 3324148
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Activation of Src protein tyrosine kinase plays an essential role in urocortin-mediated cardioprotection.

  2010influential reference
• 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

  2010cited by this paper
• Effect of long-term treatment with urocortin on the activity of somatic angiotensin-converting enzyme in spontaneously hypertensive rats.

  2010cited by this paper
• Urocortin 2 induces potent long-lasting inhibition of cardiac sympathetic drive despite baroreflex activation in conscious sheep.

  2010cited by this paper
• Plasma urocortin in acute myocardial infarction patients

  2010cited by this paper
• Urocortin II Induces Nitric Oxide Production Through cAMP and Ca2+ Related Pathways in Endothelial Cells

  2009cited by this paper
• Urocortin induced expression of COX‐2 and ICAM‐1 via corticotrophin‐releasing factor type 2 receptor in rat aortic endothelial cells

  2009cited by this paper
• A novel corticotropin‐releasing factor receptor splice variant exhibits dominant negative activity: a putative link to stress‐induced heart disease

  2009cited by this paper
• Urocortin promotes the development of vasculitis in a rat model of thromboangiitis obliterans via corticotrophin‐releasing factor type 1 receptors

  2009influential reference
• Urocortin 2 Inhibits Furosemide-Induced Activation of Renin and Enhances Renal Function and Diuretic Responsiveness in Experimental Heart Failure

  2009cited by this paper
• Plasma Urocortin 1 in Human Heart Failure

  2009cited by this paper
• Differential effects of arginine methylation on diastolic dysfunction and disease progression in patients with chronic systolic heart failure.

  2008cited by this paper
• Effect of atrial natriuretic peptide on left ventricular remodelling in patients with acute myocardial infarction.

  2008cited by this paper
• Urocortin 2 infusion in human heart failure.

  2007cited by this paper
• Urocortin 2 infusion in healthy humans: hemodynamic, neurohormonal, and renal responses.

  2007cited by this paper
• Urocortin 1 administration from onset of rapid left ventricular pacing represses progression to overt heart failure.

  2007cited by this paper
• UROCORTIN 1 ADMINISTRATION FROM ONSET OF RAPID LEFT VENRICULAR PACING REPRESSES PROGRESSION TO OVERT HEART FAILURE

  2007cited by this paper
• Urocortin prevents mitochondrial permeability transition in response to reperfusion injury indirectly by reducing oxidative stress.

  2007cited by this paper
• Plasma urocortin 1 in sheep: regional sampling and effects of experimental heart failure.

  2006cited by this paper
• Effects of intravenous urocortin on angiotensin-converting enzyme in rats.

  2006cited by this paper
• Letter regarding article by Rademaker et al, "integrated hemodynamic, hormonal, and renal actions of urocortin 2 in normal and paced sheep: beneficial effects in heart failure".

  2006cited by this paper
• Urocortin 3: haemodynamic, hormonal, and renal effects in experimental heart failure.

  2006cited by this paper
• Endothelial Urocortin Has Potent Antioxidative Properties and Is Upregulated by Inflammatory Cytokines and Pitavastatin

  2006cited by this paper
• Urocortin induces interleukin-6 gene expression via cyclooxygenase-2 activity in aortic smooth muscle cells.

  2006cited by this paper
• Effects of urocortin II on neonatal rat cardiac myocytes and non-myocytes.

  2005cited by this paper
• In vivo protective effects of urocortin on ischemia-reperfusion injury in rat heart via free radical mechanisms.

  2005cited by this paper
• Integrated Hemodynamic, Hormonal, and Renal Actions of Urocortin 2 in Normal and Paced Sheep: Beneficial Effects in Heart Failure

  2005cited by this paper
• Four-day urocortin-I administration has sustained beneficial haemodynamic, hormonal, and renal effects in experimental heart failure.

  2005cited by this paper
• Cardioprotection mediated by urocortin is dependent upon PKCε activation

  2005cited by this paper
• Expression of urocortin III/stresscopin in human heart and kidney.

  2004cited by this paper
• Hypotensive effects of ovine and human corticotrophin-releasing factors in man

  2004cited by this paper
• Plasma urocortin in human systolic heart failure.

  2004cited by this paper
• 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.

  2004cited by this paper
• The cardiovascular physiologic actions of urocortin II: acute effects in murine heart failure.

  2004cited by this paper
• 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.

  2004cited by this paper
• Protective effects of the urocortin homologues stresscopin (SCP) and stresscopin-related peptide (SRP) against hypoxia/reoxygenation injury in rat neonatal cardiomyocytes.

  2003cited by this paper
• Vasodilative Effects of Urocortin II via Protein Kinase A and a Mitogen-activated Protein Kinase in Rat Thoracic Aorta

  2003cited by this paper
• Cardiac expression of urocortin (Ucn) in diseased heart; preliminary results on possible involvement of Ucn in pathophysiology of cardiac diseases

  2003cited by this paper
• Urocortin-related peptides increase interleukin-6 output via cyclic adenosine 5'-monophosphate-dependent pathways in A7r5 aortic smooth muscle cells.

  2003cited by this paper
• Minireview: natriuretic peptides during development of the fetal heart and circulation.

  2003cited by this paper
• Relaxation of rat arteries by urocortin: effects of gender and diabetes

  2003cited by this paper
• Urocortin has cell-proliferative effects on cardiac non-myocytes

  2003cited by this paper
• Expression of urocortin and corticotropin-releasing factor receptor subtypes in the human heart.

  2002cited by this paper
• Relaxation by urocortin of human saphenous veins

  2002cited by this paper
• Beneficial hemodynamic, endocrine, and renal effects of urocortin in experimental heart failure: comparison with normal sheep.

  2002cited by this paper
• Urocortin has cell-proliferative effects on cardiac non-myocytes.

  2002cited by this paper
• Urocortin promotes hemodynamic and bioenergetic recovery and improves cell survival in the isolated rat heart exposed to ischemia/reperfusion.

  2002cited by this paper
• Activation of protein kinase B/Akt by urocortin is essential for its ability to protect cardiac cells against hypoxia/reoxygenation-induced cell death.

  2002cited by this paper
• Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor

  2001cited by this paper
• Urocortin II: A member of the corticotropin-releasing factor (CRF) neuropeptide family that is selectively bound by type 2 CRF receptors

  2001cited by this paper
• Regulation of corticotropin-releasing factor receptor type 2 beta messenger ribonucleic acid in the rat cardiovascular system by urocortin, glucocorticoids, and cytokines.

  2000cited by this paper
• Regulation of Corticotropin-Releasing Factor Receptor Type 2β Messenger Ribonucleic Acid in the Rat Cardiovascular System by Urocortin, Glucocorticoids, and Cytokines.

  2000cited by this paper
• Urocortin, a member of the corticotropin-releasing factor family, in normal and diseased heart.

  2000influential reference
• Urocortin Protects against Ischemic and Reperfusion Injury via a MAPK-dependent Pathway*

  2000cited by this paper
• Abnormal adaptations to stress and impaired cardiovascular function in mice lacking corticotropin-releasing hormone receptor-2

  2000cited by this paper
• Urocortin, a newly identified corticotropin-releasing factor-related mammalian peptide, stimulates atrial natriuretic peptide and brain natriuretic peptide secretions from neonatal rat cardiomyocytes.

  1998cited by this paper
• Expression and protective effects of urocortin in cardiac myocytes.

  1998cited by this paper
• Cardiac inotropic actions of urocortin in conscious sheep.

  1997cited by this paper
• Stimulation by corticotropin-releasing factor of atrial natriuretic peptide and brain natriuretic peptide secretions from cultured neonatal rat cardiomyocytes.

  1996cited by this paper
• Identification of a second corticotropin-releasing factor receptor gene and characterization of a cDNA expressed in heart.

  1995cited by this paper
• Identification of a novel murine receptor for corticotropin-releasing hormone expressed in the heart.

  1995cited by this paper
• A sauvagine/corticotropin-releasing factor receptor expressed in heart and skeletal muscle.

  1995cited by this paper
• Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor

  1995cited by this paper
• CRF2 alpha and CRF2 beta receptor mRNAs are differentially distributed between the rat central nervous system and peripheral tissues.

  1995cited by this paper
• Cloning and characterization of a functionally distinct corticotropin-releasing factor receptor subtype from rat brain.

  1995cited by this paper
• Effect of corticotropin releasing factor on atrial natriuretic peptide release from the isolated perfused rat heart.

  1994cited by this paper
• Effects of corticotropin-releasing factor on isolated rat heart activity.

  1993cited by this paper
• Dilatory and Inotropic Effects of Corticotropin-Releasing Factor (CRF) on the Isolated Heart

  1992cited by this paper
• Effect of corticotropin-releasing factor on the electrical and mechanical activities of the guinea-pig ventricular myocardium

  1991cited by this paper
• Effect of corticotropin-releasing factor on the electrical and mechanical activities of the guinea-pig ventricular myocardium.

  1990cited by this paper
• CRF-evoked bradycardia in urethane-anesthetized rats is blocked by naloxone.

  1985cited by this paper
• Corticotropin-releasing factor (CRF): mechanism to elevate mean arterial pressure and heart rate.

  1983cited by this paper
• Corticotropin-releasing factor (CRF): central effects on mean arterial pressure and heart rate in rats.

  1982cited by this paper
• Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin.

  1982cited by this paper
• Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin

  1981cited by this paper

• Urocortin attenuates myocardial fibrosis in diabetic rats via the Akt/GSK-3β signaling pathway

  2016cites this paper
• Urocortin ameliorates diabetic cardiomyopathy in rats via the Akt/GSK-3β signaling pathway

  2015cites this paper
• Secretion of urocortin I by human glioblastoma cell lines, possibly via the constitutive pathway.

  2015cites this paper
• Cardioprotection of 17β-estradiol against hypoxia/reoxygenation in cardiomyocytes is partly through up-regulation of CRH receptor type 2.

  2014cites this paper