Paras Kumar Mishra
University of Nebraska Medical Center, USA
Scientific Tracks Abstracts: J Diabetes Metab
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.
Paras Kumar Mishra has completed his BSc and MS in Biological Science with specialization in Zoology from India. His PhD dissertation was from Banaras Hindu University (a reputed university in India) on understanding the genetic basis of speciation. His Postdoctoral works was basically on cardiac physiology from USA. He is also interested in investigating the role of extracellular matrix (ECM) and matrix metalloproteinases (MMPs) in heart failure. The long term goal of his research is to discover an intervention tool to improve cardiac function in pathological heart using microRNAs and stem cells.
Email: paraskumar.mishra@unmc.edu
