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

Abstract :

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.

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Journal articles
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Submitted on : Friday, November 4, 2016 - 2:03:45 PM
Last modification on : Sunday, June 24, 2018 - 1:24:02 PM

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Ludovit Paulis, Jeremy Fauconnier, Olivier Cazorla, Jérome Thireau, Raffaella Soleti, et al.. Activation of Sonic hedgehog signaling in ventricular cardiomyocytes exerts cardioprotection against ischemia reperfusion injuries. Scientific Reports, Nature Publishing Group, 2015, 5, pp.7983. ⟨http://www.nature.com/srep/2015/150123/srep07983/full/srep07983.html⟩. ⟨10.1038/srep07983⟩. ⟨hal-01392497⟩

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