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 addition 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 observed 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, increased mono-nucleation, decreased multi-nucleation, and increased cm proliferation in 210-tg hearts in contrast to wild-type (ntg). likewise, myocardial infarction (mi) was created in adult mice, echocardiography was performed, and the hearts were harvested for immunohistochemistry and molecular studies. compared to ntg, 210-tg hearts showed a significant increase in cm proliferation, reduced apoptosis, upregulated angiogenesis, 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 adult mice via promoting cm proliferation, cell survival, and angiogenesis.