Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs

E. Hergenreider, S. Heydt, K. Treguer, T. Boettger, A.J.G. Horrevoets, A.M. Zeiher, M.P. Scheffer, A.S. Frangakis, X.K. Yin, M. Mayr, T. Braun, C. Urbich, R.A. Boon, S. Dimmeler

Research output: Contribution to journalArticleAcademicpeer-review

936 Citations (Scopus)


The shear-responsive transcription factor Krüppel-like factor 2 (KLF2) is a critical regulator of endothelial gene expression patterns induced by atheroprotective flow. As microRNAs (miRNAs) post-transcriptionally control gene expression in many pathogenic and physiological processes, we investigated the regulation of miRNAs by KLF2 in endothelial cells. KLF2 binds to the promoter and induces a significant upregulation of the miR-143/145 cluster. Interestingly, miR-143/145 has been shown to control smooth muscle cell (SMC) phenotypes; therefore, we investigated the possibility of transport of these miRNAs between endothelial cells and SMCs. Indeed, extracellular vesicles secreted by KLF2-transduced or shear-stress-stimulated HUVECs are enriched in miR-143/145 and control target gene expression in co-cultured SMCs. Extracellular vesicles derived from KLF2-expressing endothelial cells also reduced atherosclerotic lesion formation in the aorta of ApoE(-/-) mice. Combined, our results show that atheroprotective stimuli induce communication between endothelial cells and SMCs through an miRNA- and extracellular-vesicle-mediated mechanism and that this may comprise a promising strategy to combat atherosclerosis.

Original languageEnglish
Pages (from-to)249-256
Number of pages8
JournalNature cell biology
Issue number3
Publication statusPublished - 12 Feb 2012


  • Animals
  • Aorta/metabolism
  • Apolipoproteins E/deficiency
  • Atherosclerosis/genetics
  • Cells, Cultured
  • Coculture Techniques
  • Endothelial Cells/cytology
  • Exosomes/metabolism
  • Gene Expression Regulation/drug effects
  • Human Umbilical Vein Endothelial Cells/cytology
  • Humans
  • Kruppel-Like Transcription Factors/genetics
  • Lovastatin/analogs & derivatives
  • Mice
  • Mice, Knockout
  • MicroRNAs/genetics
  • Microscopy, Confocal
  • Microscopy, Electron
  • Myocytes, Smooth Muscle/cytology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction/genetics
  • Stress, Mechanical
  • Transfection

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