Isosorbide dinitrate improves the efficacy of bone mesenchymal stem cell transplantation via endothelial nitric oxide synthase-dependent mechanism

Abstract

This study investigated the effect of treatment wientry isosorbide dinitrate (Isoket) on bone mesenchymal stem cell (BMSC) transplantation in a rat model of myocardial infarction (MI) and its possible mechanism. Sprague-Dawley (SD) rats were randomized to a sham operation group, MI control group, BMSC transplantation group, and Isoket-BMSCs transplantation group. Isosorbide dinitrate (Isoket, 5 μg/m) was administered by intraperitoneal injection (10 ml/kg) at 0, 12, and 24 hours following ischemia/reperfusion induction of MI models. Left ventricular function, myocardial infarct size (MIS), the survival of engrafted BMSCs, and expression of vascular endothelial growentry factor (VEGF), inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) proteins were detected 2 weeks post-transplantation. The results showed isosorbide dinitrate attenuated cardiac dysfunction, increased the survival of engrafted cells in the ischemic heart and promoted iNOS, eNOS, and VEGF protein expression. It is suggested that isosorbide dinitrate enhances mesenchymal stem cell therapy for MI via an eNOS-dependent mechanism.