Referenced in: none

Automatically associated channels: Cav1.2

Title: Antiarrhythmic effect of growth factor-supplemented cardiac progenitor cells in chronic infarcted heart.

Authors: Monia Savi, Leonardo Bocchi, Stefano Rossi, Caterina Frati, Gallia Graiani, Costanza Lagrasta, Michele Miragoli, Elisa Di Pasquale, Giuliano G Stirparo, Giuseppina Mastrototaro, Konrad Urbanek, Antonella De Angelis, Emilio Macchi, Donatella Stilli, Federico Quaini, Ezio Musso

Journal, date & volume: Am. J. Physiol. Heart Circ. Physiol., 2016 Jun 1 , 310, H1622-48

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/26993221

Abstract
c-Kit(pos) cardiac progenitor cells (CPCs) represent a successful approach in healing the infarcted heart and rescuing its mechanical function, but electrophysiological consequences are uncertain. CPC mobilization promoted by hepatocyte growth factor (HGF) and IGF-1 improved electrogenesis in myocardial infarction (MI). We hypothesized that locally delivered CPCs supplemented with HGF + IGF-1 (GFs) can concur in ameliorating electrical stability of the regenerated heart. Adult male Wistar rats (139 rats) with 4-wk-old MI or sham conditions were randomized to receive intramyocardial injection of GFs, CPCs, CPCs + GFs, or vehicle (V). Enhanced green fluorescent protein-tagged CPCs were used for cell tracking. Vulnerability to stress-induced arrhythmia was assessed by telemetry-ECG. Basic cardiac electrophysiological properties were examined by epicardial multiple-lead recording. Hemodynamic function was measured invasively. Hearts were subjected to anatomical, morphometric, immunohistochemical, and molecular biology analyses. Compared with V and at variance with individual CPCs, CPCs + GFs approximately halved arrhythmias in all animals, restoring cardiac anisotropy toward sham values. GFs alone reduced arrhythmias by less than CPCs + GFs, prolonging ventricular refractoriness without affecting conduction velocity. Concomitantly, CPCs + GFs reactivated the expression levels of Connexin-43 and Connexin-40 as well as channel proteins of key depolarizing and repolarizing ion currents differently than sole GFs. Mechanical function and anatomical remodeling were equally improved by all regenerative treatments, thus exhibiting a divergent behavior relative to electrical aspects. Conclusively, we provided evidence of distinctive antiarrhythmic action of locally injected GF-supplemented CPCs, likely attributable to retrieval of Connexin-43, Connexin-40, and Cav1.2 expression, favoring intercellular coupling and spread of excitation in mended heart.