MiR-126 promotes endothelial cell apoptosis by targeting PI3K/Akt in rats with lower limb arteriosclerosis obliterans

W.-M. Li, J.-N. Yue, D.-Q. Guo, W.-G. Fu

Department of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. fu.weiguo@zs-hospital.sh.cn

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• Geriatrics

OBJECTIVE: To investigate the influence of micro ribonucleic acid (miR)-126 on the rats with lower limb arteriosclerosis obliterans (ASO).

MATERIALS AND METHODS: Male Sprague- Dawley rats aged 3 months old were randomly divided into Sham operation group (Control group, n=10) and Model group (n=10), and the model of lower limb ASO was established. After modeling, the expression of miR-126 in arteries was detected using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), and the change in the downstream signaling pathway was examined via Western blotting. The human umbilical vein endothelial cells (HUVECs) were induced by oxidized low-density lipoprotein (Ox-LDL) to establish the model of endothelial injury, followed by detection of miR-126 expression. Then, the Luciferase assay was performed to verify the downstream target gene of miR-126. After being cultured, HUVECs were set as Control group, Ox-LDL induction group, and Ox-LDL + miR-126 inhibitor group, and the expressions of phosphorylated-protein kinase B (p-Akt) and cleaved cysteine-aspartic protease-3 (Caspase-3) were detected in the above groups.

RESULTS: After the establishment of the model, the expression level of miR-126 was raised in vessels, but the phosphatidylinositol 3-hydroxy kinase (PI3K)/Akt signals were weakened (p<0.01). Ox-LDL-induced endothelial cell apoptosis promoted the expression of miR-126, and the difference was statistically significant. The bioinformatics analysis results showed that PI3KR2 was a direct target of miR-126, which was also proven via the Luciferase assay. Moreover, the transfection with miR-126 inhibitor into endothelial cells suppressed Ox-LDL-induced cell apoptosis, thereby persistently activating the PI3K/Akt signaling pathway (p<0.01).

CONCLUSIONS: In rats with lower limb arteriosclerosis obliterans (ASO), miR-126 represses the PI3K/Akt signaling pathway to accelerate endothelial cell apoptosis.

Published on: 2019/08/07

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