Rapamycin promoted thrombosis and platelet adhesion to endothelial cells by inducing membrane remodeling.
Rapamycin promoted thrombosis and platelet adhesion to endothelial cells by inducing membrane remodeling.
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雷帕霉素通过诱导膜重塑促进血栓形成和血小板与内皮细胞的粘附
DOI：
10.1186/1471-2121-15-7
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发表时间：
2014-02-24
期刊：
影响因子：
--
通讯作者：
Cai JP
中科院分区：
文献类型：
--
作者：
Jiang P;Lan Y;Luo J;Ren YL;Liu DG;Pang JX;Liu J;Li J;Wang C;Cai JP
背景近年来，有证据表明，全球范围内广泛使用的雷帕霉素洗脱支架可能会增加血栓形成的风险。相反，其他研究人员发现它是安全的。因此，有必要阐明雷帕霉素对血栓形成的影响及其机制。结果雷帕霉素的作用通过改良的深静脉血栓动物模型进行评价。血小板来自健康志愿者，并评估培养的内皮细胞中的血小板-内皮（购自ATCC）粘附。共聚焦显微镜和电子显微镜观察内皮细胞膜皱褶。在注射雷帕霉素的大鼠中血栓形成增加。电子显微镜分析显示雷帕霉素处理的大鼠内皮细胞上的微绒毛。雷帕霉素增强人脐静脉内皮细胞（HUVECs）的膜皱褶和血小板与HUVECs的粘附。细胞松弛素B可抑制HUVECs与血小板的粘附。自噬抑制3-甲基腺嘌呤导致抑制膜皱褶在HUVECs和增强platelet-endothelial adhesion.ConclusionsIn结论，我们发现，由雷帕霉素诱导的内皮细胞膜重塑是至关重要的血小板粘附到内皮细胞，从而为血栓形成invivo，和内皮细胞膜重塑是自噬依赖。
BackgroundRecently, evidence indicated that the rapamycin-eluting stent which was used worldwide may contribute to an increased risk for thrombosis. On the contrary, other researchers found it was safe. Thus, it is necessary to clarify the effect of rapamycin on thrombosis and the corresponding mechanisms.ResultsThe effects of rapamycin invivowere evaluated by modified deep vein thrombosis animal model. The platelets were from healthy volunteers and the platelet-endothelium (purchased from ATCC) adhesion in cultured endothelial cells was assessed. Membrane rufflings in endothelial cells were examined by confocal and electron microscope. Thrombus formation increased in rats that were injected with rapamycin. Electron microscope analysis exhibited microvilli on the rapamycin-treated endothelium in rats. Rapamycin enhanced membrane ruffling in human umbilical vein endothelial cells (HUVECs) and adhesion of platelets to HUVECs. The platelet-HUVECs adhesion was attenuated when cells were treated with cytochalacin B. Inhibition of autophagy by 3-methyladenine led to suppression of membrane ruffles in HUVECs and augmentation of platelet-endothelial adhesion.ConclusionsIn conclusion, we found that endothelial membrane remodeling induced by rapamycin is crucial for the adhesion of platelets to endothelial cells and thereby for thrombosis invivo, and that the endothelial membrane remodeling is autophagy dependent.
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