一个机械传感复合体,它调解了内皮细胞对流体剪切应激反应的反应
Eleni Tzima1, Mohamed Irani-Tehrani, William B Kiosses
1Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Nature
|September 16, 2005
概括
血小板内皮细胞粘附分子-1 (PECAM-1) 和其他受体形成一个复合体,感知血流. 这一途径对于动脉样硬化的早期阶段至关重要.
科学领域:
- 血管生物学 血管生物学
- 机械转导是指机械转导的过程.
- 心血管研究的心血管研究.
背景情况:
- 剪切应激对血管平衡至关重要,影响重塑,心脏发育和动脉动脉产生.
- 整合素激活调解了一些剪切应力反应,但上游机制仍然不清楚.
研究的目的:
- 为了研究分子路径上游的整合素激活,以应对剪切应力.
- 为了确定参与血管内皮细胞机械传导的关键受体.
主要方法:
- 研究了PECAM-1,血管内皮细胞干素和VEGFR2在形成机械传感复合物的作用.
- 评估了这些受体的足够性,以赋予异质细胞的流动响应性.
- 利用PECAM-1-淘汰赛小鼠研究体内对干扰流量的反应.
主要成果:
- 鉴定了一种机械感应复合体,包括PECAM-1,血管内皮细胞素和VEGFR2.
- 证明这个复合体足以赋予非血管细胞的流动响应性.
- 显示PECAM-1-淘汰赛小鼠未能激活NF-kappaB和炎症基因在扰乱的流动区域.
结论:
- 一个涉及PECAM-1,VE-cadherin和VEGFR2的新型机械感知途径调解了剪切应力反应.
- 这一途径对于在动脉生成中最早发生的分子事件至关重要.
- 了解这种途径为血管平衡和疾病发展提供了新的见解.
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