Abstract 16314: Identification of MicroRNAs Inducing Adult Cardiomyocyte Proliferation
Background: Even though neonatal cardiomyocytes (NCM) proliferate robustly, adult cardiomyocytes (ACM) have very little proliferative potential. By functional screening of 875 microRNAs (miRs) Eulalio et al 2012 identified 46 miRs which induce proliferation of NCMs by more than 35%. Additional studies by Mahmood et al 2013 have identified Meis1 as the major player that controls ACM cell cycle. We hypothesize that the proliferation inducing potential of miRs may vary between NCMs and ACMs and some of these miRs may induce proliferation through Meis1 regulation.
Methods and Results: ACM were isolated from male rats aged 4-6 months and transfected with miR mimics for cel-67 (control) and 24 of the top NCM proliferation inducing miRs individually. Edu was administered for 4 days starting day 1 after transfection. Cells were fixed on day 5 and immuno-stained. Proliferating cardiomyocytes were identified by co-staining of TnI and Edu and the percentage was calculated in each group. Eighteen of the 24 miRs induced significant proliferation of ACMs . The most significant of them with more than 7% increase in ACM proliferation were miR-302b-5p (7.8±0.6), miR-1910 (9.8±0.76), miR-548c-3p (11.9±2.7), miR-2053 (10.1±0.4), miR-936 (11.6±3.4), miR-1825 (54±5.2), miR-509 (7.1±0.62), miR-590 (11.5±1.1) and miR-23b-3p (12.7±0.35). Of these we identified 3 miRs (miR-548c-3p, miR-509-3p and miR-23b) to have binding site on the 3’UTR of Meis1 and simultaneously showing an increase in proliferation. Meis1 has been established as a critical transcriptional regulator of CM proliferation through activation of CDK inhibitors.
Conclusion: To the best of our knowledge this is the first study to identify a panel of miRs inducing ACM proliferation. Delivering these miRs to the infarcted region is a promising approach and has the potential to regenerate the ischemic heart by inducing proliferation of CMs surrounding the infarct zone.
Author Disclosures: R. Pandey: None. L. Jackson: None. G. Ma: None. R.P. Ahmed: None.
- © 2014 by American Heart Association, Inc.