Analysis of cardiac miRNA expression in the early neonatal period

ABSTRACT: The regenerative capacity of the mammalian heart is lost quickly after birth when cardiomyocytes stop dividing and undergo cell cycle arrest. Thus, the adult mammalian heart lacks the ability to heal itself to any appreciable amount after ischemic injury such as myocardial infarction. Heart growth begins during fetal life with the first phase of DNA synthesis that is exclusively associated with cardiomyocyte proliferation. This process proceeds until 12 hours after birth and is defined as 0 days in our submitted samples. Cardiomyocytes division is undetectable at neonatal day 1. To analyze the molecular mechanisms responsible for cessation of cardiomyocyte proliferation, we performed genome-wide miRNA microarray profiling by comparing postnatal days 0 vs 1d.This revealed a profile of 8 significantly downregulated miRNAs in the proliferative DKO hearts (versus vehicle-injected control), that were enriched for mRNA targets involved in cell cycle regulation. In vitro studies have demonstrated that knockdown of these 8 miRNAs in neonatal rat cardiomyocytes can increase the occurrence of cytokinetic events. Ultimately, we aim to inject antagomirs targeting these miRNAs into mice post-myocardial infarction to determine the effect of these miRNAs on heart function and cardiomyocyte proliferation in vivo.

ORGANISM(S): Mus musculus

SUBMITTER: Ludger Hauck 

PROVIDER: E-MTAB-9256 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress