[Olmesartan inhibits age-associated migration and invasion of human aortic vascular smooth muscle cells by upregulating miR-3133 axis].

ABSTRACT: OBJECTIVE:To explore the effects of olmesartan on age-associated migration and invasion capacities and microRNA (miRAN) axis in human aortic vascular smooth muscle cells (HA-VSMCs). METHODS:Cultured HA-VSMCs were divided into control group, bleomycin-mediated senescence (BLM) group and bleomycin + olmesartan treatment group. Wound-healing assay and Boyden chambers invasion assay were used to assess the changes in migration and invasion of the cells, gelatin zymography was used to analyze matrix metalloproteinase-2 (MMP-2) activation in the cells. The differentially expressed miRNAs were identified by miRNA microarray assay and validated by quantitative real-time PCR. MiR-3133 inhibitor was used to examine the effects of molecular manipulation of olmesartan on age-associated migration and invasion and MMP-2 activation in the cells. RESULTS:Compared with those of the control group, the percentage of the repopulated cells and the number of cells crossing the basement membrane increased significantly in BLM group [(78.43±12.76)% vs (42.47±7.22)%, P < 0.05; 33.33±5.51 vs 13.00±4.36, P < 0.05]. A significant increase of MMP-2 activation was found in BLM group as compared with the control group (1.66 ± 0.27 vs 0.87 ± 0.13, P < 0.05). Olmesartan significantly inhibited BLM-induced enhancement of cell migration and invasion and MMP-2 secretion in the cells. MiR-3133 was significantly downregulated in BLM group and upregulated in olmesartan group. Transfection with miR-3133 inhibitor significantly reversed the effects of olmesartan on age-associated migration and invasion of the cells [(85.87±7.39)% vs (49.77±3.05)%; 34.67±2.31 vs 20.00±4.58, P < 0.05] and MMP-2 activation in the cells (1.76±0.19 vs 0.94±0.10, P < 0.05). CONCLUSIONS:Olmesartan inhibits the migration and invasion of ageassociated HA-VSMCs probably by upregulating of the miR-3133 axis.

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC7225100 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature