MicroRNA-210-mediated proliferation, survival, and angiogenesis promote cardiac repair post myocardial infarction in rodents

An innovative approach for cardiac regeneration following injury is to induce endogenous cardiomyocyte (CM)cell cycle re-entry. In the present study, CMs from adult rat hearts were isolated and transfected with cel-miR-67 (control) and rno- miR-210. A significant increase in CM proliferation and mono-nucleation were observed in miR-210 group, in addi- tion to a reduction in CM size, multi-nucleation, and cell death. When compared to control, β-catenin and Bcl-2 were upregulated while APC (adenomatous polyposis coli), p16, and caspase-3 were downregulated in miR-210 group. In silico analysis predicted cell cycle inhibitor, APC, as a direct target of miR-210 in rodents.Moreover, compared to control, a significant increase in CM survival and proliferation were ob- served with siRNA-mediated inhibition of APC. Furthermore, miR-210 overexpressing C57BL/6 mice (210-TG) were used for short-term ischemia/reperfusion study, revealing smaller cell size, increasedmono-nucleation, decreased multi-nucleation, and increased CMproliferation in 210-TG hearts in contrast to wild- type (NTG). Likewise,myocardial infarction (MI) was created in adult mice, echocardiography was performed, and the heart were harvested forimmunohistochemistry andmolecular studies. Compared to NTG, 210-TG hearts showed a significant increase in CM proliferation, reduced apoptosis, upregulated angiogene- sis, reduced infarct size, and overall improvement in cardiac function following MI. β-catenin, Bcl-2, and VEGF (vascular endothelial growth factor) were upregulated while APC, p16, and caspase-3 were downregulated in 210-TG hearts. Overall, constitutive overexpression of miR-210 rescues heart function following cardiac injury in adultmice via promoting CM prolif- eration, cell survival, and angiogenesis.