Up‐regulation of miR‐195 contributes to cardiac hypertrophy‐induced arrhythmia by targeting calcium and potassium channels

Previous studies have confirmed that miR‐195 expression is increased in cardiac hypertrophy, and the bioinformatics website predicted by Targetscan software shows that miR‐195 can directly target CACNB1, KCNJ2 and KCND3 to regulate Cavβ1, Kir2.1 and Kv4.3 proteins expression. The purpose of this study is to confirm the role of miR‐195 in arrhythmia caused by cardiac hypertrophy. The protein levels of Cavβ1, Kir2.1 and Kv4.3 in myocardium of HF mice were decreased. After miR‐195 was overexpressed in neonatal mice cardiomyocytes, the expression of ANP, BNP and β‐MHC was up‐regulated, and miR‐195 inhibitor reversed this phenomenon. Overexpression of miR‐195 reduced the estimated cardiac function of EF% and FS% in wild‐type (WT) mice. Transmission electron microscopy showed that the ultrastructure of cardiac tissues was damaged after miR‐195 overexpression by lentivirus in mice. miR‐195 overexpression increased the likelihood of arrhythmia induction and duration of arrhythmia in WT mice. Lenti‐miR‐195 inhibitor carried by lentivirus can reverse the decreased EF% and FS%, the increased incidence of arrhythmia and prolonged duration of arrhythmia induced by TAC in mice. After miR‐195 treatment, the protein expressions of Cavβ1, Kir2.1 and Kv4.3 were decreased in mice. The results were consistent at animal and cellular levels, respectively. Luciferase assay results showed that miR‐195 may directly target CACNB1, KCNJ2 and KCND3 to regulate the expression of Cavβ1, Kir2.1 and Kv4.3 proteins. MiR‐195 is involved in arrhythmia caused by cardiac hypertrophy by inhibiting Cavβ1, Kir2.1 and Kv4.3.