Catherine A Makarewich1, Constantine D Troupes1, Sarah M Schumacher2, Polina Gross1, Walter J Koch2, David L Crandall3, Steven R Houser4. 1. Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA; Department of Physiology, Temple University School of Medicine, Philadelphia, PA 19140, USA. 2. Center for Translational Research, Temple University School of Medicine, Philadelphia, PA 19140, USA; Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140, USA. 3. Janssen Research & Development, LLC, Spring House, PA 19044, USA. 4. Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA; Department of Physiology, Temple University School of Medicine, Philadelphia, PA 19140, USA. Electronic address: srhouser@temple.edu.
Abstract
RATIONALE: There is a current need for the development of new therapies for patients with heart failure. OBJECTIVE: We test the effects of members of the corticotropin-releasing factor (CRF) family of peptides on myocyte contractility to validate them as potential heart failure therapeutics. METHODS AND RESULTS: Adult feline left ventricular myocytes (AFMs) were isolated and contractility was assessed in the presence and absence of CRF peptides Urocortin 2 (UCN2), Urocortin 3 (UCN3), Stresscopin (SCP), and the β-adrenergic agonist isoproterenol (Iso). An increase in fractional shortening and peak Ca(2+) transient amplitude was seen in the presence of all CRF peptides. A decrease in Ca(2+) decay rate (Tau) was also observed at all concentrations tested. cAMP generation was measured by ELISA in isolated AFMs in response to the CRF peptides and Iso and significant production was seen at all concentrations and time points tested. CONCLUSIONS: The CRF family of peptides effectively increases cardiac contractility and should be evaluated as potential novel therapeutics for heart failure patients.
RATIONALE: There is a current need for the development of new therapies for patients with heart failure. OBJECTIVE: We test the effects of members of the corticotropin-releasing factor (CRF) family of peptides on myocyte contractility to validate them as potential heart failure therapeutics. METHODS AND RESULTS: Adult feline left ventricular myocytes (AFMs) were isolated and contractility was assessed in the presence and absence of CRF peptides Urocortin 2 (UCN2), Urocortin 3 (UCN3), Stresscopin (SCP), and the β-adrenergic agonist isoproterenol (Iso). An increase in fractional shortening and peak Ca(2+) transient amplitude was seen in the presence of all CRF peptides. A decrease in Ca(2+) decay rate (Tau) was also observed at all concentrations tested. cAMP generation was measured by ELISA in isolated AFMs in response to the CRF peptides and Iso and significant production was seen at all concentrations and time points tested. CONCLUSIONS: The CRF family of peptides effectively increases cardiac contractility and should be evaluated as potential novel therapeutics for heart failurepatients.
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