MiR 20a 5p overexpression prevented diabetic cardiomyopathy via inhibition of cardiomyocyte apoptosis, hypertrophy, fibrosis, and JNK/NF kB signaling pathway.
Diabetic cardiomyopathy (DCM) is a common cardiovascular disease. A declined miR 20a 5p was observed in hearts of diabetic mice, while its effect on DCM remains unknown. Herein, we established streptozotocin induced DCM rat model and high glucose stimulated H9C2 model of DCM. They then were treated with adenovirus expressing miR 20a 5p to explore the function of miR 20a 5p. ITT and ipGTT assay revealed that miR 20a 5p reduced blood glucose level. Besides, miR 20a 5p improved cardiac dysfunction reflected by reduced HW/BW and LVDP, and increased LVSP and LV dp/dt max. MiR 20a 5p prevented cardiomyocyte apoptosis, along with the up regulated c caspase 3, bax and down regulated bcl 2. Moreover, miR 20a 5p alleviated cardiac hypertrophy as the parameters of ANP, BNP and MyHC b decreased. Also, miR 20a 5p attenuated the cardiac fibrosis demonstrated by decreased TGF b1, collagen I levels and the inflammatory response manifested by reduced IL 6, TNF a and IL 1b production. Furthermore, miR 20a 5p prevented JNK phosphorylation and NF kB p65nuclear translocation. Similarly, the effects of miR 20a 5p on DCM were confirmed in our in vitro experiments. Additionally, ROCK2 is a possible target gene of miR 20a 5p. ROCK2 overexpression reversed the protective effect of miR 20a 5p on DCM. Overall, miR 20a 5p may effectively ameliorate DCM through improving cardiac metabolism, and subsequently inhibiting inflammation, apoptosis, hypertrophy, fibrosis, and JNK/NF kB pathway via modulating ROCK2.
Journal of biochemistry