MicroRNA-208a Dysregulates Apoptosis Genes Expression and Promotes Cardiomyocyte Apoptosis during Ischemia and Its Silencing Improves Cardiac Function after Myocardial Infarction

Abstract EN

Aims.

miR-208a is associated with adverse outcomes in several cardiac pathologies known to have increased apoptosis, including myocardial infarction (MI).

We investigated if miR-208a has proapoptotic effects on ischemic cardiomyocytes and if its silencing has therapeutic benefits in MI.

Methods and Results.

The effect of miR-208a on apoptosis during ischemia was studied in cultured neonatal mice myocytes transfected with agomir or antagomir.

Differential gene expression was assessed using microarrays.

MI was induced in male C57BL/6 mice randomly assigned to antagomir ( n = 6 ) or control group ( n = 7 ), while sham group ( n = 7 ) had sham operation done.

Antagomir group received miR208a antagomir, while control and sham group mice received vehicle only.

At 7 and 28 days, echocardiography was done and thereafter hearts were harvested for analysis of apoptosis by TUNEL method, fibrosis using Masson’s trichrome, and hypertrophy using hematoxylin and eosin.

miR-208a altered apoptosis genes expression and increased apoptosis in ischemic cardiomyocytes.

Therapeutic inhibition of miR-208a decreased cardiac fibrosis, hypertrophy, and apoptosis and significantly improved cardiac function 28 days after MI.

Conclusion.

miR-208a alters apoptosis genes expression and promotes apoptosis in ischemic cardiomyocytes, and its silencing attenuates apoptosis, fibrosis, and hypertrophy after MI, with significant improvement in cardiac function.