Induction of autophagy markers is associated with attenuation of miR-133a in diabetic heart failure patients undergoing mechanical unloading.

Authors

Shyam Sundar Nandi, University of Nebraska Medical CenterFollow
Michael J. Duryee, University of Nebraska Medical CenterFollow
Hamid R. Shahshahan, University of Nebraska Medical CenterFollow
Geoffrey M. Thiele, University of Nebraska Medical CenterFollow
Daniel R. Anderson, University of Nebraska Medical CenterFollow
Paras K. Mishra, University of Nebraska Medical CenterFollow

Document Type

Article

Journal Title

American Journal of Translational Research

Publication Date

Spring 4-15-2015

Volume

7

Abstract

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.

ISSN

1943-8141

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

Recommended Citation

Nandi, Shyam Sundar; Duryee, Michael J.; Shahshahan, Hamid R.; Thiele, Geoffrey M.; Anderson, Daniel R.; and Mishra, Paras K., "Induction of autophagy markers is associated with attenuation of miR-133a in diabetic heart failure patients undergoing mechanical unloading." (2015). Journal Articles: Cellular & Integrative Physiology. 9.
https://digitalcommons.unmc.edu/com_cell_articles/9