Advanced Glycation End Products Activate the mi RNA /RhoA/ ROCK 2 Pathway in Endothelial Cells

Objective AGE s induce endothelial cell dysfunction in HUVEC s, resulting in ROS production and triggering apoptosis. This study sought to identify mi RNA s involved in AGE ‐induced endothelial cell injury. Methods Microarray analysis to identify mi RNA s altered with AGE stimulation was undertaken, and results were confirmed using real‐time quantitative polymerase chain reaction . The interaction of mi RNA s with the RhoA and ROCK 2 genes was confirmed using luciferase assays, and their effects on expression were determined using Western blot analysis. The effects of AGE s and mi RNA s on endothelial cell permeability were assessed. Results AGE s induced ROS production and apoptosis of HUVEC s ( p  <   0.05). AGE ‐induced miR‐200b and miR‐200c downregulation led to increased expression of their target genes, RhoA and ROCK , respectively. AGE ‐induced endothelial cell permeability and F‐actin expression were significantly reduced with both miR‐200b and miR‐200c mimics ( p  <   0.05). Furthermore, AGE ‐induced stress fiber formation was reduced in cells treated with miR‐200b mimics. Conclusion miR‐200b and miR‐200c are suppressed in AGE ‐induced endothelial cell injury, resulting in unregulated RhoA/ ROCK 2 signaling. Further studies are necessary to evaluate the therapeutic value of targeting mi RNA s or their target genes for treatment of vascular diseases.