Activation of Sonic hedgehog signaling in ventricular cardiomyocytes exerts cardioprotection against ischemia reperfusion injuries.

Autor: Paulis L; UMR CNRS 9214, Inserm U1046, Université de Montpellier, CHRU Montpellier, Montpellier, France., Fauconnier J; UMR CNRS 9214, Inserm U1046, Université de Montpellier, CHRU Montpellier, Montpellier, France., Cazorla O; UMR CNRS 9214, Inserm U1046, Université de Montpellier, CHRU Montpellier, Montpellier, France., Thireau J; UMR CNRS 9214, Inserm U1046, Université de Montpellier, CHRU Montpellier, Montpellier, France., Soleti R; INSERM U1063, Stress oxydant et pathologies métaboliques, LUNAM Université, Angers, France., Vidal B; UMR CNRS 9214, Inserm U1046, Université de Montpellier, CHRU Montpellier, Montpellier, France., Ouillé A; UMR CNRS 9214, Inserm U1046, Université de Montpellier, CHRU Montpellier, Montpellier, France., Bartholome M; UMR CNRS 9214, Inserm U1046, Université de Montpellier, CHRU Montpellier, Montpellier, France., Bideaux P; UMR CNRS 9214, Inserm U1046, Université de Montpellier, CHRU Montpellier, Montpellier, France., Roubille F; UMR CNRS 9214, Inserm U1046, Université de Montpellier, CHRU Montpellier, Montpellier, France., Le Guennec JY; UMR CNRS 9214, Inserm U1046, Université de Montpellier, CHRU Montpellier, Montpellier, France., Andriantsitohaina R; INSERM U1063, Stress oxydant et pathologies métaboliques, LUNAM Université, Angers, France., Martínez MC; INSERM U1063, Stress oxydant et pathologies métaboliques, LUNAM Université, Angers, France., Lacampagne A; UMR CNRS 9214, Inserm U1046, Université de Montpellier, CHRU Montpellier, Montpellier, France.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2015 Jan 23; Vol. 5, pp. 7983. Date of Electronic Publication: 2015 Jan 23.
DOI: 10.1038/srep07983
Abstrakt: Sonic hedgehog (SHH) is a conserved protein involved in embryonic tissue patterning and development. SHH signaling has been reported as a cardio-protective pathway via muscle repair-associated angiogenesis. The goal of this study was to investigate the role of SHH signaling pathway in the adult myocardium in physiological situation and after ischemia-reperfusion. We show in a rat model of ischemia-reperfusion that stimulation of SHH pathway, either by a recombinant peptide or shed membranes microparticles harboring SHH ligand, prior to reperfusion reduces both infarct size and subsequent arrhythmias by preventing ventricular repolarization abnormalities. We further demonstrate in healthy animals a reduction of QTc interval mediated by NO/cGMP pathway leading to the shortening of ventricular cardiomyocytes action potential duration due to the activation of an inward rectifying potassium current sharing pharmacological and electrophysiological properties with ATP-dependent potassium current. Besides its effect on both angiogenesis and endothelial dysfunction we demonstrate here a novel cardio-protective effect of SHH acting directly on the cardiomyocytes. This emphasizes the pleotropic effect of SHH pathway as a potential cardiac therapeutic target.
Databáze: MEDLINE
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