H2S inhibits atrial fibrillation-induced atrial fibrosis through miR-133a/CTGF axis

Abstract

AimAtrial fibrillation (AF) is a common clinical arrhythmia and can cause a variety of complications. To study the therapeutic effect of H2S in atrial fibrosis and explore the important role of miR-133a, in vitro experiments in human atrial fibroblasts (HAFs) were conducted. MethodsThe fibrosis in HAFs was induced by Ang II. The expression levels of miR-133a and CTGF in HAFs were examined by qRT-PCR. The proliferation and migration of HAFs were detected by CCK-8 and cell scratch assays. The protein expressions of CTGF, collagen I, collagen III and α-SMA were detected by western blotting. The dual-luciferase reporter gene was used to detect the interaction between miR-133a and CTGF. ResultsThe proliferation and migration of HAFs stimulated by Ang II were enhanced, the expression of miR-133a was reduced, and the levels of CTGF and fibrosis markers (collagen I, collagen III and α-SMA) were increased. Furthermore, H2S reduced fibrosis, proliferation and migration of HAFs induced by Ang II. Accordingly, overexpression of miR-133a inhibited the proliferation and migration ability on Ang II-induced HAFs, and decreased the protein expressions of related fibrosis markers and CTGF. Meanwhile, miR-133a inhibitor could reverse the inhibition effect of H2S on proliferation and migration in HAFs by Ang II-induced. By targeting CTGF, miR-133a inhibited the expression of CTGF. ConclusionH2S improved myocardial cell fibrosis by significantly increasing the expression of miR-133a, and CTGF might be a potential target for miR-133a to play an important role in myocardial fibrosis.