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Nat Cell Bio:miRNA传输方式可防止动脉硬化

来源:中国科学报 2012-02-21 21:47

近日,国外科学家在国际杂志《自然—细胞生物学》NATURE CELL BIOLOGY上的一篇文章中指出,他们发现两种血管细胞可通过小型非编码RNA相互传递信息以减少动脉硬化。由于动脉硬化与心脏病发作和中风等严重健康问题有密切联系,因此该发现将在动脉硬化相关治疗中起重要作用。

局部血流中的差异性可防止动脉中一定区域发生动脉硬化。这种针对动脉硬化的保护机制由存在于血管内皮细胞中的转录因子KLF2所主导。

Stefanie Dimmeler和同事发现,KLF2能够上调内皮细胞中名为miR-143/145的miRNA的表达量。他们还注意到,如果将血管壁平滑肌细胞与内皮细胞混合培养,内皮细胞会释放一种含有miR-143/145、被称为“微泡”的包膜小分子,随后平滑肌细胞将这种微泡吸收掉。通过这种细胞间的微泡调节传输,内皮细胞中的miR-143/145可实现对平滑肌细胞中基因表达的调控。此外,研究人员还进一步证明了对患有动脉硬化的小鼠注射含有miR-143/145的微泡,会减少小鼠体内动脉硬化病变的形成。

该项研究发现意味着,动脉硬化疗法的研究或可利用内皮细胞和平滑肌细胞之间的这种miRNA传输。(生物谷Bioon.com)

Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs

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

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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