Astragaloside IV inhibits angiotensin II-induced aortic dissection formation by regulating miR-320a/matrix metallopeptidase 9 axis

Abstract

This study explored the role of miR-320a and Matrix metallopeptidase 9 (MMP-9) in aortic dissection (AD) formation. Aortic tissue diameter (LD) and medial thickness (MT) were measured after the AD model was established. Aortic smooth muscle cells (VSMCs) were assigned into blank group, Astragaloside IV (AS-IV), which was treated with 100, 150 or 200 μg/mL and AngII group. Cells in the AngII group were added with MMP9 inhibitor (MMP9 inhibitor group) and mimics (MMP9 mimics group), followed by analysis of cell proliferation, apoptosis, and target gene for miR-320a. Aortic tissue diameter(LD) from the AD group was significantly higher and MT was lower than in the control group (p<0.05). VSMCs proliferative activity in the AS-IV group and AngII group was increased significantly (p <0.05), with lower activity in the AS-IV group than AngII group (p < 0.05). After transfection, the VSMCs apoptosis in the AngII group was decreased (p <0.05). In addition, cell migration in the AS-IV and AngII groups increased (p <0.05), with lower ability in the AS-IV group than in the AngII group (p <0.05). Alpha smooth muscle Actin (α-SMA) expression was elevated after AngII stimulation and decreased after AS-IV treatment (p <0.05). After AngII stimulation, miR-320a and MMP9 were upregulated (p <0.05) and downregulated by AS-IV (p <0.05). MMP9 is a target gene for miR-320a. miR-320a and MMP9 expressions in the AS-IV group were significantly decreased, with lowest levels in the AS-IV-200 μg/mL group. In addition, MMP9 overexpression reduced the AngII expression. The expression of miR-320a/MMP9 axis was low in the AD, and activity were increased after AngII stimulation. In conclusion, As-IV can relieve the occurrence of AD via regulation of miR-320a/MMP9 axis.