Paras Kumar Mishra
University of Nebraska Medical Center, USA
Title: MicroRNA autophagy axis in diabetic hearts
Biography
Biography: Paras Kumar Mishra
Abstract
Diabetes is a complex multifactorial disease that increases the incident of heart failure. However, the underlying molecular mechanism of diabetic heart failure is unclear. Diabetic hearts show down-regulation of several cardioprotective miRNAs including the most abundant miRNA in the heart, the miR-133a. Recently, we demonstrated that in diabetic heart failure patients, down-regulation of miR-133a is associated with up-regulation of cardiac autophagy. We hypothesized that attenuation of miR-133a in diabetic hearts induces cardiac autophagy. To test the hypothesis, we treated Insulin2 mutant (Ins2+/-) diabetic Akita mice, which show down-regulated miR-133a in the heart with miR-133a mimic and measured the level of autophagy markers in the heart. To determine the cellular mechanism, we also treated HL1 cardiomyocytes with high glucose and miR-133a mimic and measured the level of autophagy markers. Further, we treated these cells with Bafilomycin A1 to assess autophagy flux. Our results demonstrated that miR-133a mimic treatment normalized the up-regulated autophagy in hyperglycemic cardiomyocytes. These in vitro findings were supported by the in vivo results, where miR-133a mimic treatment restored autophagy markers in Akita hearts. We conclude that miR-133a plays pivotal role in regulating autophagy in diabetic hearts.