Abstract 008: Bone Marrow Mesenchymal Stem Cells Prevented Cardiac Arrhythmias Of Infarcted Heart Via Regulating Calcineurin And Potassium Channels Expression
Bone marrow mesenchymal stem cells (BMSCs) emerge as a new promising approach for treating heart diseases. However, the effects of BMSCs-based therapy on cardiac electrophysiological remodeling following myocardial infarction were largely unclear. This study was aimed to investigate whether BMSCs transplantation prevented cardiac arrhythmias in post-infarcted hearts. Myocardial infarction was established in male SD rats, and BMSCs were then intramyocardially transplanted into the infarcted hearts after 3 days. Cardiac electrophysiological remodeling in the border zone was evaluated by western blotting and whole-cell path clamp technique after 2 weeks. We found that BMSCs transplantation significantly ameliorated the increased heart weight index, the impaired left ventricular functions, and the enhanced cardiac fibrosis in infarcted hearts. The survival ratio of infarcted rats was also improved after BMSCs transplantation. Importantly, electrical stimulation-induced arrhythmias were seldom observed in BMSCs-transplanted infarcted rats compared with rats without BMSCs treatment. Furthermore, BMSCs transplantation effectively inhibited the prolongation of action potential duration and the reduction of transient and sustained outward potassium currents in ventricular myocytes from post-infarcted rats. Consistently, BMSCs-transplanted infarcted hearts exhibited the more expression of KV4.2, KV4.3, KV1.5 and KV2.1 proteins than infarcted hearts. Moreover, intracellular free calcium level, calcineurin and nuclear NFATc3 protein expression was shown activated in infarcted hearts, which was inhibited after BMSCs transplantation. Collectively, BMSCs transplantation prevented ventricular arrhythmias by reversing the reduction of cardiac potassium channels in post-infarcted heats, which involves attenuated intracellular calcium overload and calcineurin/NFATc3 signal pathway.
- © 2013 by American Heart Association, Inc.