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

Atherosclerosis. 2011 Aug;217(2):326-30. doi: 10.1016/j.atherosclerosis.2011.03.034. Epub 2011 Apr 5.

Abstract

Background: Increasing evidence has demonstrated that the senescence of vascular endothelial cells has 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 complementary sequences in the 3'UTR of their target mRNAs. MiRs modulate a variety of biological functions such as cell development, cell differentiation, and apoptosis. Moreover, several miRs involved in endothelial cell function have been identified.

Methods and results: Through a microarray approach, we have identified a miR-146a that is progressively modulated in endothelial cells with aging. In young human umbilical vein endothelial cells, this miR is 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Cellular Senescence / genetics*
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Enzymologic
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Humans
  • MicroRNAs / metabolism*
  • NADPH Oxidase 4
  • NADPH Oxidases / genetics
  • NADPH Oxidases / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • RNA, Messenger / metabolism
  • Transfection

Substances

  • MIRN146 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • NADPH Oxidase 4
  • NADPH Oxidases
  • NOX4 protein, human