Induction of endogenous regenerative capacity has emerged as one promising approach to repair damaged hearts following myocardial infarction (MI). Re-expression of factors that are exclusively expressed during embryonic development may reactivate the ability of adult cardiomyocytes to regenerate. Here, we identified miR-411 as a potent inducer of cardiomyocyte proliferation. Overexpression of miR-411 in the heart significantly increased cardiomyocyte proliferation and survival in a model MI. We found that miR-411 enhances the activity of YAP, the main downstream effector of the Hippo pathway, in cardiomyocytes. In conclusion, miR-411 induces cardiomyocyte regeneration and improves cardiac function post-MI likely by modulating the Hippo/YAP pathway.
Keywords: CVEC, cardiac vascular endothelial cells; EdU, 5-ethynyl-2'-deoxyuridine; Hippo pathway; LAD, left anterior descending coronary artery; MI, myocardial infarction; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NFAT, nuclear factor of activated T cells; NRCF, neonatal rat cardiac fibroblast; NRCM, neonatal rat cardiomyocytes; PCR, polymerase chain reaction; PEI, polyethylenimine; cTnI, cardiac troponin I; cardiac remodeling; heart failure; miRNA, microRNA; microRNA-411; myocardial infarction; pHH3, phosphohistone H3; qPCR, quantitative PCR.
© 2022 The Authors.