miR-146a is modulated in human endothelial cell with aging

Background: Increasing evidence has demonstrated that the senescence of vascular endothelial cellshas critical roles in the pathogenesis of vascular dysfunction such as atherosclerosis and thrombosis.MicroRNA (miR) are small non-coding RNAs that inhibit gene expression by binding to complementarysequences in the 3UTR of their target mRNAs. MiRs modulate a variety of biological functions such ascell development, cell differentiation, and apoptosis. Moreover, several miRs involved in endothelial cellfunction have been identified.Methods and results: Through a microarray approach, we have identified a miR-146a that is progressivelymodulated in endothelial cells with aging. In young human umbilical vein endothelial cells, this miRis involved in a premature senescence-like phenotype through direct targeting of the NOX4 protein,implicated in cell senescence and aging.Conclusions and general significance: Finding important factors that regulate endothelial cell senescence,like miR-146a, will help provide novel therapeutic strategies for vascular disorders.