Elucidation of Therapeutic Potential of Down Regulated mi-RNA In Diabetes Linked Cardiac Hypertrophy Involved In Regulation of Mitochondrial Centered Signaling

Abstract

Diabetes Mellitus refers to a group of metabolic disorders characterized by high blood sugar levels. The rising incidence of diabetes and associated cardiovascular diseases are becoming significant global health concern. There is urgent need to develop a therapeutic strategy to combat the rising prevalence of diabetes. The current study was designed to examine the therapeutic potential of miRNA-137-3p in mitigating the effects of diabetes linked cardiac hypertrophy and to understand the role of mitochondrial centred signaling in this process. Baseline characteristics and histological analysis showed miRNA-137-3p had a cardio-protective effect. The administration of STZ+miRNA-137-3p antagomir led to a decrease in ROS and an increase in anti-oxidative enzymes compared to the group treated with streptozotocin. The mitochondrial membrane potential was found to be elevated in STZ+miRNA 137-3p antagomir as compared to the streptozotocin treated group. There was also significant reduction in the mitochondrial ROS as compared to the streptozotocin group. The qRT-PCR revealed that miRNA-137-3p was upregulated in the streptozotocin group however, administration of STZ+miRNA-137-3p antagomir reduced the expression of miRNA137-3p. The expression of PGC-1α, a target of miRNA137-3p, was downregulated in the streptozotocin group, whereas upon miRNA-137-3p antagomir treatment its expression was upregulated and normalize its downstream targets i.e., Drp-1, Mfn-2 and PINK-1. MiRNA-137-3p also normalized the ANP and BNP expression levels, which were high in STZ treated group. Moreover, results also showed that miRNA-137-3p antagomir had a cardio-protective effect as it decreased the expression of Bcl-2 and increased the level of Bax. In conclusion, these findings demonstrate the potential of miRNA-137-3p antagomir as a therapeutic strategy in treating diabetes linked cardiac hypertrophy. However, further advanced studies are required to employ miRNA-137-3p as a treatment in various cardiovascular diseases.