Abstract

Cardio vascular disease (CVD), particularly myocardial infarction (MI) is the major cause of morbidity and mortality in the world wide. The majority of CVD cases occur in patients with underlying acute or chronic heart disease. The incidence of MI increases in the presence of diabetes and increase further in the presence of structural heart disease. It has been recognized that diabetics experience a greater mortality during the acute phase MI and a higher morbidity in the post‐MI period. To improve regeneration of the injured myocardium, it is necessary to enhance the intrinsic capacity of the heart to regenerate itself and/or replace the damaged tissue by cell regeneration. Several studies have demonstrated that microRNAs (miRs) are important for stem cell maintenance and differentiation via translational repression. miR‐499 was produced almost exclusively in the heart. We hypothesize that miR‐499 improves post‐MI condition in diabetic mice via regenerating myocytes and promoting new vessels toward the damaged part, improving myocytes contractility and ejection function. Mdivi‐1 improves miR‐499 in heart post‐MI, which inhibits mitophagy in cardiomyocyte through decreasing Drp‐1 accumulation in mitochondria. Our data shows that miR‐499 regulates the mitochondrial fission, contractility was improved for 34±3% in treated mice. New vessles were formed from ligated part toward the MI part, and ejection fraction was increased for 18±2 % compared to untreated mice. Based on our data we suggest that modulation of miR‐499 levels may provide a therapeutic approach for treating Heart failure in the presence of structural heart defect during diabetes.