The Role and Mechanism of circAMOTL1 in Hypertensive Heart Failure

Abstract

To explore the changes of circAMOTL1 expression, cell function and expression of fibrosis-related proteins in myocardial hypertrophy and fibrosis model. Human cardiomyocytes AC16 were cultured, and the concentration of Ang II was firstly explored by CCK-8. After determining the optimal dose of Ang II, AC16 cells were induced to construct an in vitro model of myocardial hypertrophy and fibrosis. CCK-8 was utilized to assess cell proliferation. Flow cytometry was performed to validate cell cycle and apoptosis. circAMOTL1, miR-330-3p, smad7, Col1a2 and Col3a1 genes expressions were assessed by qRT-PCR. smad7, Col1a2 and Col3a1 proteins expressions were evaluated using Western blot and IF. FISH was performed to detect circAMOTL1 localization in cells. 10 μM Ang II was selected for subsequent experiments. Compared with control group, cell viability of the Ang II group was significantly decreased, apoptosis was observably increased, circAMOTL1 and smad7 expressions were signally repressed, miR-330-3p, Col1a2 and Col3a1 expressions were notably increased. Both circAMOTL1 and miR-330-3p, miR-330-3p and smad7 had targeted binding sites. Overexpression of circAMOTL1 promoted AC16 cells proliferation and inhibited apoptosis. In addition, overexpression of circAMOTL1 inhibited miR-330-3p and promoted smad7 expression. Overexpression of circAMOTL1 inhibited miR-330-3p and promoted smad7 expression. circAMOTL1 may be a potential target for treating hypertensive heart failure.