Exploring the cardioprotective potential of mi-RNA by regulation of PGC1α associated signaling

Abstract

Cardiovascular diseases (CVDs) are highly prevalent around the world with a high morbidity and mortality rate. Despite the speed of technological advancement in the pharmacological interventions area, cardiac pathological hypertrophy is still an independent factor, leading to death among CVDs. MicroRNAs are highly versatile molecule and act as key regulators in various cellular mechanism. They have the potential to develop new therapeutic strategies. The current research was conducted to investigate the therapeutic potential of miR-137-3p in cardiac hypertrophy and to understand the regulation of PGC-1α, a transcriptional coactivator and its downstream signaling pathway. To achieve the projected goal, rats were divided into four different groups i.e., control group, isoproterenol (ISO) treated group, ISO+NC (negative control) and ISO+miR-137 3p Antagomir group. After the dissection of rats biochemical analysis, qRT-PCR and mitochondrial assay were performed. Results from biochemical analysis showed an increase in reactive oxygen species (ROS) and decrease in anti-oxidative enzymes level in isoproterenol treated group which were reversed upon administration of miR-137-3p Antagomir. MIR-137-3p was upregulated in ISO treated group which was evaluated by qRT-PCR. PGC-1α, a putative target of miR-137-3p was downregulated at transcription level in isoproterenol administered group. After the administration of miR-137-3p Antagomir, the expression level of miR-137-3p was downregulated however, the PGC-1α level was normalized. MiR-137-3p also normalized the expression of downstream signaling modulators of PGC-1α, such as Drp-1, Mfn-2 and Bcl-2 regulate multiple cellular signaling including mitochondrial biogenesis, switching of fuel metabolism, mitochondrial dynamics etc, and indirectly ANP and BNP expression levels, which were high in ISO treated group. Administration of miR-137-3p Antagomir was also instrumental in attenuating the mitochondrial membrane potential and mitochondrial-derived ROS, thus suggesting its cardioprotective potential. These findings suggest the cardio-protective role of miR-137-3p in cardiac hypertrophy by regulation of PGC-1. So, miRNAs can be used as a potent therapeutic strategy with some advancement to treat the cardiac diseases