MiR-29a regulates cardiomyocyte apoptosis by targeting Bak1 in diabetic cardiomyopathy.

Abstract

This study sought to investigate the association between microRNA-29a (miR-29a) and cardiomyocyte apoptosis in diabetic cardiomyopathy (DCM). DCM rat model was established by treating rats with streptozotocin (STZ), followed by injection of NC or miR-29a-3p mimics into the myocardium of rats. High glucose (HG)-treated H9c2 cells were transfected with NC and miR-29a-3p mimics. DCM rats presented elevated levels of blood glucose, HbA1c, blood pressure, urine output, decreased body weight and cardiac contractile function after modeling. MiR-29a was lowly expressed in STZ-treated rats and HG-treated H9c2 cells. Upregulation of miR-29a improved cardiac structure and function and attenuated, alleviated myocardial histological abnormalities and fibrosis and lowered cardiomyocyte apoptosis in DCM rats. Meanwhile, HG promoted H9c2 cell apoptosis, while miR-29a overexpression attenuated the function of HG. Compared with control group, the protein expression of Bax, cleaved-caspase3 and Bak1 in DCM and HG groups were significantly upregulated, and the expression of Bcl-2 and Mcl-1 was downregulated, while miR-29a overexpression exerted opposite effect. Bioinformatics prediction method and western blot revealed that miR-29a directly targeted Bak1 and downregulated Bak1 expression. Overall, miR-29a regulated STZ- and HG-induced cardiomyocyte apoptosis by targeting Bak1, providing a novel understanding of the pathogenesis of DCM.