Key result
Up-regulation of miR-195 contributes to cardiac hypertrophy-induced arrhythmia and reduced cardiac function by directly targeting and inhibiting Cavβ1, Kir2.1, and Kv4.3 channels in mice.
Why the study?
Although miR-195 expression increases in cardiac hypertrophy and is predicted to target calcium and potassium channel genes, its specific role in cardiac hypertrophy-induced arrhythmia required confirmation.
Does miR-195 overexpression or inhibition regulate cardiac hypertrophy-induced arrhythmia and ion channel expression in mice?
Does miR-195 overexpression or inhibition regulate cardiac hypertrophy-induced arrhythmia and ion channel expression in mice?
miR-195 promotes cardiac hypertrophy-induced arrhythmia by downregulating calcium and potassium channels (Cavβ1, Kir2.1, and Kv4.3), suggesting it as a potential therapeutic target.
miR-195 may promote hypertrophy-related arrhythmia in mice; hypothesis-generating for human therapeutic targeting.
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.
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Xuan et al. (2020) studied Cardiac hypertrophy-induced arrhythmia. miR-195 overexpression and inhibition vs. Wild-type controls was evaluated on Cardiac function (EF% and FS%), arrhythmia induction and duration, and protein expression. Up-regulation of miR-195 contributes to cardiac hypertrophy-induced arrhythmia and reduced cardiac function by directly targeting and inhibiting Cavβ1, Kir2.1, and Kv4.3 channels in mice.
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