慢性生理剪切应激抑制瘤缩因子诱导的炎症反应在子大动脉透ex vivo
Hideyuki Yamawaki1, Stephanie Lehoux, Bradford C Berk
1Center for Cardiovascular Research, Box 679, 601 Elmwood Ave, University of Rochester, Rochester, NY 14642, USA.
Circulation
|September 10, 2003
概括
物理剪切应激,像层状流一样,通过抑制特定的信号通路来减少血管炎症. 这项研究表明,正常的剪切应力可以防止瘤缩因子-α诱导的内皮细胞的炎症反应.
科学领域:
- 心血管生物学 心血管生物学
- 血管炎症 血管炎症
- 机械转导是指机械转导的过程.
背景情况:
- 动脉样硬化较少发生在暴露于稳定层状流动的血管系统中,而不是扰乱的流动.
- 以前的研究表明,短期的层状流动抑制了内皮细胞 (EC) 中的瘤缩因子 (TNF) - α介导的炎症信号传递.
- 生理剪切应力的动脉动脉保护作用背后的机制尚不清楚.
研究的目的:
- 为了研究慢性剪切应激对TNF-α诱导的炎症反应的影响.
- 阐明剪切应力调节血管炎症的分子机制.
主要方法:
- 使用子主动脉的ex vivo perfusion器官培养系统.
- 暴露于低 (0.4 dyne/cm2) 或正常 (12 dyne/cm2) 的切割应力24-26小时.
- 选择性净化EC和血管光滑肌细胞 (VSMC) 蛋白质;分析TNF-α诱导的VCAM-1表达和MAP激酶激活.
主要成果:
- 低剪压特别刺激了血管细胞粘附分子 (VCAM) - 1表达在EC中,但不是VSMC,在TNF-alpha暴露后.
- 接受正常剪切应力的预暴露显著抑制了TNF-α诱导的ECs中的VCAM-1表达.
- 正常的剪切应激抑制了EC中c-Jun NH2-终端激酶 (JNK) 和p38 MAP激酶的TNF-α激活,并阻止了TNF受体 (TNFR) -1与TNFR相关因子 (TRAF) -2的关联.
结论:
- 生理上的剪切应力表现出抗炎性质.
- 它特别抑制内皮细胞中MAP激酶信号通路 (JNK,p38).
- 它还抑制了TNFR-1和TRAF-2之间的相互作用,有助于减少炎症.
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