Autophagy is ubiquitous in all forms of
heart failure and cardioprotective miR-133a is attenuated in human
heart failure. Previous reports from
heart failure patients undergoing left
ventricular assist device (LVAD) implantation demonstrated that autophagy is upregulated in the LV of the failing human heart. Studies in the murine model show that diabetes downregulates miR-133a. However, the role of miR-133a in the regulation of autophagy in diabetic hearts is unclear. We tested the hypothesis that diabetes exacerbates cardiac autophagy by inhibiting miR-133a in
heart failure patients undergoing LVAD implantation. The
miRNA assay was performed on the LV of 15 diabetic (D) and 6 non-diabetic (ND)
heart failure patients undergoing LVAD implantation. Four ND with highly upregulated and 5 D with highly downregulated miR-133a were analyzed for autophagy markers (
Beclin1, LC3B, ATG3) and their upstream regulators (mTOR and AMPK), and
hypertrophy marker (
beta-myosin heavy chain) by RT-qPCR, Western blotting and immunofluorescence. Our results demonstrate that attenuation of miR-133a in diabetic hearts is associated with the induction of autophagy and
hypertrophy, and suppression of mTOR without appreciable difference in AMPK activity. In conclusion, attenuation of miR-133a contributes to the exacerbation of diabetes mediated cardiac autophagy and
hypertrophy in
heart failure patients undergoing LVAD implantation.