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To test the hypothesis that inhibition of miR-133a induces mitophagy in diabetic hearts and it is ameliorated by overexpression of miR-133a, we used four in vivo groups: C57BL/6J, Akita (T1D), Akita+miR-133a, and Akita+scramble; and four in vitro groups of HL1 cardiomyocytes: low (LG-5mM), high (HG-25mM) doses of D-glucose, HG+miR-133a, and HG+scramble; and determined mitoSOX generation, depolarization of damaged mitochondria (ΔΨ, by JC-1), mitochondrial fission (by DRP1 and Parkin), autophagosome formation (by Beclin1, ATG14, ATG3, LC3B) and its lysosomal degradation (by RFP-GFP-LC3B) using qPCR, Western blotting, immunofluorescence, and transmission electron microscopy (TEM). Our results demonstrate that in HG cardiomyocytes, mitoSOX generation, depolarization of mt-ΔΨ and DRP1 protein are elevated by 2.5±0.3, 1.44±0.08 and 1.94±0.29 folds, respectively, but ameliorated (mitoSOX:4.9±0.04, mt-ΔΨ:2.11±0.08, and DRP1:0.85±0.17 fold down regulation) by overexpression of miR-133a. The levels of Beclin1, ATG1...

Activation of renin-angiotensin system (RAS) within the paraventricular nucleus (PVN) of the hypothalamus has been suggested to enhance sympathetic activation in chronic heart failure (CHF) condition. The contribution due to changes in angiotensinogen (AGT) per se remains to be examined. In this study, we observed a 12-fold increase in levels of AGT gene in the PVN of CHF rats compared to sham-operated controls. In order to elucidate the molecular mechanism for increased expression of AGT, we performed in silico analysis of 3'-UTR of AGT gene and found potential binding site for microRNA (miR)-133a. We found a 1.9-fold decrease in mir-133a expression in the PVN of rats with CHF. We hypothesized that decreased expression of mir-133a may be responsible for the increased expression of AGT in the PVN. To test this hypothesis we used NG108 (neuroblastoma x glioma) cell line, which endogenously expresses RAS, as our in vitro model. Overexpression of miR133a (pEZX-MR03-miR133a) in NG108 cells resulted in 1.4 and...

Although Mdivi-1 ameliorates heart failure by inhibiting autophagy, the mechanism of Mdivi-1 mediated mitigation of cardiac dysfunction in diabetes is unclear. We hypothesize that Mdivi-1 improves ...

Optimum level of autophagy is indispensable for survival and cellular function, and miRNA tightly regulates biological functions. In diabetic hearts, miR-133a (anti-hypertrophy and anti-fibrosis) i...

Inhibition of microRNA (miR)-133a causes cardiac hypertrophy and fibrosis. However, the beneficial effects of miR-133a in cardiac dysfunction remain to be examined. Furthermore, impaired contractil...