Investigating the Therapeutic Potential of miRNA-137-3p/383-5p/PGC-1α Signalling Nexus Against Cardiac Hypertrophy

Pathological growth of cardiomyocytes known as cardiac hypertrophy (CH). Differential expressions of miRNAs have an immense therapeutic potential against cardiac hypertrophy. The current study aim is to evaluate the therapeutic potential of miRNA-137-3p/383-5p in cardiac hypertrophy by regulation of PGC-1α signaling nexus. Silencing of pro-hypertrophic miRNAs e.g. miR-137-3p and miR-383-5p leads to the restoration of their common target gene PGC-1α in hypertrophic cells. Interestingly, the results of this invivo study showed the cardioprotective effects of these antagomirs. Moreover, PGC-1α associated signaling events e.g. fatty acid oxidation (Cpt1a, Cpt1b), mitochondria membrane potential (MMP), mitochondrial reactive oxygen species (mtROS), oxidative phosphorylation (Ndufa6, Atp5me), apoptosis (Bcl-2, BAX), antioxidants (SOD, GSH, CAT), mitochondrial dynamic (Mfn-2, Drp-1) were significantly restored in the treated groups of miRNA antagomirs. Conclusively, this study uncovers that the pharmacological inhibition of miR-137-3p and miR-383-5p have a potential to rescue from the cardiac hypertrophy by regulation of PGC-1α signaling nexus.