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血小板衍生的微颗粒通过 miR-142-3p 促进高血压患者内皮细胞的增殖。

Platelet-derived microparticles promote endothelial cell proliferation in hypertension via miR-142-3p.

机构信息

Institute of Mechanobiology and Medical Engineering, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

出版信息

FASEB J. 2018 Jul;32(7):3912-3923. doi: 10.1096/fj.201701073R. Epub 2018 Feb 26.

Abstract

Endothelial cells (ECs) are located at the interface between flowing blood and the vessel wall, and abnormal EC proliferation induced by pathologic environments plays an important role in vascular remodeling in hypertensive conditions. Exchanges of information between blood components and ECs are important for EC function. Hence, the present study sought to determine how platelets induce EC dysfunction under hypertensive conditions. EC proliferation was increased in renal hypertensive rats established by abdominal aortic coarctation compared with control rats and that elevated thrombin in plasma promoted platelet activation, which may induce the release of platelet-derived microparticles (PMPs). MicroRNA (MiR) array and qPCR revealed a higher level of miR-142-3p in platelets and PMPs. In vitro, PMPs delivered miR-142-3p into ECs and enhanced their proliferation via Bcl-2-associated transcription factor (BCLAF)1 and its downstream genes. These results indicate that PMPs deliver miR-142-3p from activated platelets into ECs and that miR-142-3p may play important roles in EC dysfunction in hypertensive conditions and may be a novel therapeutic target for maintaining EC homeostasis in hypertension.-Bao, H., Chen, Y.-X., Huang, K., Zhuang, F., Bao, M., Han, Y., Chen, X.-H., Shi, Q., Yao, Q.-P., Qi, Y.-X. Platelet-derived microparticles promote endothelial cell proliferation in hypertension via miR-142-3p.

摘要

内皮细胞(ECs)位于血流和血管壁之间的界面,病理环境引起的异常 EC 增殖在高血压条件下的血管重塑中起着重要作用。血液成分与 EC 之间的信息交换对于 EC 功能很重要。因此,本研究旨在确定血小板在高血压条件下如何诱导 EC 功能障碍。与对照组大鼠相比,腹主动脉缩窄建立的肾性高血压大鼠的 EC 增殖增加,且血浆中升高的凝血酶促进血小板活化,这可能诱导血小板衍生的微颗粒(PMP)释放。微阵列和 qPCR 显示血小板和 PMP 中 miR-142-3p 水平升高。在体外,PMP 将 miR-142-3p 递送至 EC 并通过 Bcl-2 相关转录因子(BCLAF)1 及其下游基因增强其增殖。这些结果表明,活化的血小板将 PMP 中的 miR-142-3p 递送至 EC,miR-142-3p 可能在高血压条件下的 EC 功能障碍中发挥重要作用,并且可能成为维持高血压 EC 动态平衡的新的治疗靶点。-包,H.,陈,Y.-X.,黄,K.,庄,F.,宝,M.,韩,Y.,陈,X.-H.,石,Q.,姚,Q.-P.,齐,Y.-X. 血小板衍生的微颗粒通过 miR-142-3p 促进高血压中的内皮细胞增殖。

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