title: Catestatin improves post-ischemic left ventricular function and decreases ischemia/reperfusion injury in heart.
abstract: The Chromogranin A (CgA)-derived anti-hypertensive peptide catestatin (CST) antagonizes catecholamine secretion, and is a negative myocardial inotrope acting via a nitric oxide-dependent mechanism. It is not known whether CST contributes to ischemia/reperfusion injury or is a component of a cardioprotective response to limit injury. Here, we tested whether CST by virtue of its negative inotropic activity improves post-ischemic cardiac function and cardiomyocyte survival. Three groups of isolated perfused hearts from adult Wistar rats underwent 30-min ischemia and 120-min reperfusion (I/R, Group 1), or were post-conditioned by brief ischemic episodes (PostC, 5-cycles of 10-s I/R at the beginning of 120-min reperfusion, Group 2), or with exogenous CST (75 nM for 20 min, CST-Post, Group-3) at the onset of reperfusion. Perfusion pressure and left ventricular pressure (LVP) were monitored. Infarct size was evaluated with nitroblue-tetrazolium staining. The CST (5 nM) effects were also tested in simulated ischemia/reperfusion experiments on cardiomyocytes isolated from young-adult rats, evaluating cell survival with propidium iodide labeling. Infarct size was 61 ± 6% of risk area in hearts subjected to I/R only. PostC reduced infarct size to 34 ± 5%. Infarct size in CST-Post was 36 ± 3% of risk area (P < 0.05 respect to I/R). CST-Post reduced post-ischemic rise of diastolic LVP, an index of contracture, and significantly improved post-ischemic recovery of developed LVP. In isolated cardiomyocytes, CST increased the cell viability rate by about 65% after simulated ischemia/reperfusion. These results suggest a novel cardioprotective role for CST, which appears mainly due to a direct reduction of post-ischemic myocardial damages and dysfunction, rather than to an involvement of adrenergic terminals and/or endothelium.
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Penna
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Alloatti
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Gallo
authors.forename: Maria Carmela
authors.initials: MC
authors.lastname: Cerra
authors.forename: Renzo
authors.initials: R
authors.lastname: Levi
authors.forename: Francesca
authors.initials: F
authors.lastname: Tullio
authors.forename: Eleonora
authors.initials: E
authors.lastname: Bassino
authors.forename: Serena
authors.initials: S
authors.lastname: Dolgetta
authors.forename: Sushil K
authors.initials: SK
authors.lastname: Mahata
authors.forename: Bruno
authors.initials: B
authors.lastname: Tota
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pagliaro
mesh_terms: D000818:Animals; D002469:Cell Separation; D002470:Cell Survival; D053379:Chromogranin A / Q000494:pharmacology* / Q000627:therapeutic use; D003971:Diastole / Q000187:drug effects; D006321:Heart / Q000503:physiopathology*; D006334:Heart Function Tests / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D013599:Systole / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D053379:Chromogranin A; D010446:Peptide Fragments; C109084:chromogranin A (344-364)