Abstract 15788: IL-10 Enhances Survival and Angiogenic Properties of Intra-myocardially Injected Endothelial Progenitor Cells
Persistent inflammatory response has adverse effects on left ventricular (LV) function and remodeling following acute myocardial infarction (MI). Endothelial progenitor cells (EPC) transplantation has been shown to enhance neo-vascularization and improve post-MI ventricular functions. However, EPC survival and function in the injured myocardium is adversely influenced by hostile environment like prolonged inflammation, reduced oxygen supply and free radical damage, thereby compromising full benefits of EPC-mediated vascular repair. We hypothesized that inhibition of inflammation with anti-inflammatory cytokine IL-10 may improve EPC survival and function and therefore enhance EPC-mediated attenuation of LV dysfunction and remodeling after MI. GFP-labeled EPC were injected intramyocardially after induction of MI, and the mice were treated with either saline or recombinant IL-10. Inflammatory response (at 3 days) and LV functional and structural remodeling changes (at 14 and 28 days, post-MI) were evaluated. At 3 days post-MI, the number of EPC that were available in the myocardium was higher in IL-10 treated mice as compared to untreated group. IL-10 significantly reduced apoptosis of EPC in the myocardium at 3 days post-MI. Echocardiography showed injection of EPC increased percent fractional shortening and ejection fraction compared to control mice. Interestingly, LV function was significantly improved in mice receiving EPC+IL-10 compared to EPC alone. These changes corroborated with significant increase in EPC-associated capillaries coupled with enhanced STAT3 activation in the LV of IL-10 treated mice. microRNA array analysis of LPS-treated EPC has indicated significant increases in a number of survival and angiogenesis-related miRNAs including miR-21, -20b, -375, -298, -672). Taken together, our studies demonstrate that IL-10 enhances EPC survival and function leading to increased availability of viable EPCs that contributes to improved LV function and EPC-associated angiogenesis, partly mediated via activation of STAT3 signaling cascade.
- © 2010 by American Heart Association, Inc.