KLF2
细胞生物学
小RNA
生物
胞外囊泡
下调和上调
微泡
细胞外
调节器
基因表达调控
转录因子
内皮
内皮干细胞
血管平滑肌
基因
体外
生物化学
遗传学
平滑肌
内分泌学
作者
Eduard Hergenreider,Susanne Heydt,Karine Tréguer,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
摘要
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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