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

W-M Li1, J-N Yue, D-Q Guo

  • 1Department of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. fu.weiguo@zs-hospital.sh.cn.

Abstract

Insights

MicroRNA-126 (miR-126) exacerbates lower limb arteriosclerosis obliterans (ASO) by inhibiting the PI3K/Akt pathway, leading to increased endothelial cell apoptosis. Inhibiting miR-126 protects against ASO progression.

Area of Science:

  • Vascular Biology
  • Molecular Medicine
  • Biochemistry

Background:

  • Arteriosclerosis obliterans (ASO) is a significant cause of lower limb ischemia.
  • The role of microRNAs in ASO pathogenesis requires further elucidation.
  • Endothelial dysfunction is a key feature of ASO.

Purpose of the Study:

  • To investigate the role of microRNA-126 (miR-126) in the development of lower limb arteriosclerosis obliterans (ASO) in a rat model.
  • To explore the molecular mechanisms by which miR-126 influences endothelial cell apoptosis and the PI3K/Akt signaling pathway.

Main Methods:

  • ASO model established in male Sprague-Dawley rats.
  • miR-126 expression analyzed using qRT-PCR.
  • PI3K/Akt signaling pathway assessed via Western blotting.
  • Human umbilical vein endothelial cells (HUVECs) treated with oxidized low-density lipoprotein (Ox-LDL) to induce injury.
  • Luciferase assay used to identify miR-126 targets.

Main Results:

  • miR-126 expression was upregulated in ASO rat vessels, correlating with weakened PI3K/Akt signaling.
  • Oxidized low-density lipoprotein (Ox-LDL) induced endothelial cell apoptosis and increased miR-126 expression.
  • PI3K regulatory subunit 2 (PI3KR2) identified as a direct target of miR-126.
  • Inhibition of miR-126 suppressed Ox-LDL-induced apoptosis and activated the PI3K/Akt pathway.

Conclusions:

  • miR-126 plays a detrimental role in lower limb arteriosclerosis obliterans (ASO) by repressing the PI3K/Akt signaling pathway.
  • This repression by miR-126 accelerates endothelial cell apoptosis, contributing to ASO progression.
  • Targeting miR-126 may offer a therapeutic strategy for ASO.

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