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MicroRNA-210-mediated proliferation, survival, and angiogenesis promote cardiac repair post myocardial infarction in rodents
Arif, Mohammed Pandey, Raghav Alam, Perwez Jiang, Shujia Sadayappan, Sakthivel Paul, Arghya Ahmed, Rafeeq P. H.
Arif, Mohammed
Pandey, Raghav
Alam, Perwez
Jiang, Shujia
Sadayappan, Sakthivel
Paul, Arghya
Ahmed, Rafeeq P. H.
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Abstract
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.
Description
The final publication is available at Springer via http://dx.doi.org/10.1007/s00109-017-1591-8.
Date
2017-12
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Springer Verlag
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Keywords
MiR-210, Cardiomyocyte, Adenomatous polyposis coli, Myocardial infarction
Citation
Arif, M., Pandey, R., Alam, P., Jiang, S., Sadayappan, S., Paul, A., & Ahmed, R. P. H. (2017). MicroRNA-210-mediated proliferation, survival, and angiogenesis promote cardiac repair post myocardial infarction in rodents. Journal of Molecular Medicine (Berlin, Germany), 95(12), 1369–1385. http://doi.org/10.1007/s00109-017-1591-8