Inhibition of miR-92a improves re-endothelialization and prevents neointima formation following vascular injury.
Inhibition of miR-92a improves re-endothelialization and prevents neointima formation following vascular injury.
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miR-92a的抑制作用可改善重新内皮化，并防止血管损伤后新内膜形成。
DOI：
10.1093/cvr/cvu162
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发表时间：
2014-09-01
影响因子：
10.8
通讯作者：
Sedding DG
中科院分区：
文献类型：
--
作者：
Daniel JM;Penzkofer D;Teske R;Dutzmann J;Koch A;Bielenberg W;Bonauer A;Boon RA;Fischer A;Bauersachs J;van Rooij E;Dimmeler S;Sedding DG
microRNA（miR）-92a是缺血后内皮细胞增殖和血管生成的重要调节因子，但miR-92 a对血管损伤后再内皮化和新生内膜病变形成的影响尚不清楚。我们测试了使用基于特异性锁核酸（LNA）的抗miR降低miR-92 a水平以及内皮特异性敲除miR-92 a对小鼠股动脉线诱导损伤后再内皮化和新生内膜形成的影响。MiR-92 a在导丝诱导损伤后的新生内膜病变中显著上调。Pre-miR-92 a过表达导致miR-92 a直接靶基因整合素α5和sirtuin 1的抑制，并降低体外eNOS表达。MiR-92 a损害内皮细胞的增殖和迁移，但不损害平滑肌细胞。在体内，用LNA修饰的反义分子系统性抑制miR-92 a表达导致裸露血管区域的再内皮化显著加速。在主要代表内皮细胞的Tie 2表达细胞中，miR-92 a的遗传缺失增强了再内皮化，而在造血细胞中缺乏miR-92 a表达的小鼠中未观察到表型。增强的内皮恢复与损伤后21天白细胞积聚减少和新生内膜形成抑制相关，并导致miR-92 a靶点整合素α5和sirtuin 1的去抑制。我们的数据表明，抑制内皮miR-92 a通过加速再内皮化来减弱新生内膜损伤的形成，因此代表了一种推定的新机制，以增强血管损伤后的功能恢复。
MicroRNA (miR)-92a is an important regulator of endothelial proliferation and angiogenesis after ischaemia, but the effects of miR-92a on re-endothelialization and neointimal lesion formation after vascular injury remain elusive. We tested the effects of lowering miR-92a levels using specific locked nucleic acid (LNA)-based antimiRs as well as endothelial-specific knock out of miR-92a on re-endothelialization and neointimal formation after wire-induced injury of the femoral artery in mice. MiR-92a was significantly up-regulated in neointimal lesions following wire-induced injury. Pre-miR-92a overexpression resulted in repression of the direct miR-92a target genes integrin α5 and sirtuin1, and reduced eNOS expression in vitro. MiR-92a impaired proliferation and migration of endothelial cells but not smooth muscle cells. In vivo, systemic inhibition of miR-92a expression with LNA-modified antisense molecules resulted in a significant acceleration of re-endothelialization of the denuded vessel area. Genetic deletion of miR-92a in Tie2-expressing cells, representing mainly endothelial cells, enhanced re-endothelialization, whereas no phenotype was observed in mice lacking miR-92a expression in haematopoietic cells. The enhanced endothelial recovery was associated with reduced accumulation of leucocytes and inhibition of neointimal formation 21 days after injury and led to the de-repression of the miR-92a targets integrin α5 and sirtuin1. Our data indicate that inhibition of endothelial miR-92a attenuates neointimal lesion formation by accelerating re-endothelialization and thus represents a putative novel mechanism to enhance the functional recovery following vascular injury.
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DOI：
10.1161/atvbaha.110.209692
发表时间：
2010-10-01
影响因子：
8.7
作者：
Daniel, Jan-Marcus;Bielenberg, Wiebke;Sedding, Daniel G.
通讯作者：
Sedding, Daniel G.
DOI：
10.1084/jem.20052546
发表时间：
2006-12-25
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Sedding D;Daniel JM;Muhl L;Hersemeyer K;Brunsch H;Kemkes-Matthes B;Braun-Dullaeus RC;Tillmanns H;Weimer T;Preissner KT;Kanse SM
通讯作者：
Kanse SM
影响因子：
15.9
作者：
Rudic, RD;Shesely, EG;Sessa, WC
通讯作者：
Sessa, WC
影响因子：
64.8
作者：
Guarani V;Deflorian G;Franco CA;Krüger M;Phng LK;Bentley K;Toussaint L;Dequiedt F;Mostoslavsky R;Schmidt MHH;Zimmermann B;Brandes RP;Mione M;Westphal CH;Braun T;Zeiher AM;Gerhardt H;Dimmeler S;Potente M
通讯作者：
Potente M
影响因子：
20.1
作者：
Loyer, Xavier;Potteaux, Stephane;Tedgui, Alain
通讯作者：
Tedgui, Alain