Atheroprotective Communication Between Endothelial Cells and Smooth Muscle Cells Through MiRNAs

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2012 Feb 14

PMID 22327366

Citations 650

Authors

Eduard Hergenreider

Susanne Heydt

Karine Treguer

Thomas Boettger

Anton J G Horrevoets

Andreas M Zeiher

Margot P Scheffer

Achilleas S Frangakis

Xiaoke Yin

Manuel Mayr

Thomas Braun

Carmen Urbich

Reinier A Boon

Stefanie Dimmeler

Affiliations

Soon will be listed here.

Abstract

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.

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