内皮细胞特异性反应性氧物种的产生增加了对大动脉剖析的易感性
Lampson M Fan1, Gillian Douglas1, Jennifer K Bendall1
1From the BHF Centre of Research Excellence, Division of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK (L.M.F., G.D., J.K.B., E.M., M.J.C., A.B.H., M.A.M., J.E.S., R.P.L., K.M.C.); and Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK (A.M., J.-M.L.).
Circulation
|May 9, 2014
概括
内皮细胞 (EC) 的反应性氧物种 (ROS) 驱动大动脉剖析. 这项研究表明,通过环素A (CypA),EC衍生的ROS增加了大动脉壁对损伤的敏感性,突出了心血管疾病的关键机制.
科学领域:
- 心血管生物学 心血管生物学
- 血管细胞信号传递
- 氧化应激机制 氧化应激机制
背景情况:
- 心血管疾病的特征是血管壁反应性氧物种 (ROS) 的增加,但具体的细胞贡献仍然不清楚.
- 治疗策略受限于对血管细胞ROS在疾病发病过程中的不完全理解.
- 内皮细胞 (EC) ROS在结构性血管疾病中的作用需要进一步研究.
研究的目的:
- 调查内皮细胞 (EC) ROS在结构性血管疾病发展中的特定作用.
- 为了确定内皮特异性Nox2过度表达是否会影响对大动脉剖析的易感性.
- 为了阐明参与EC ROS介导的血管损伤的信号通路.
主要方法:
- 产生了一个小鼠模型,具有内皮特异性的Nox2过度表达.
- 服用血管新生II (Ang II) 诱导大动脉剖析.
- 分析了主动脉组织的ROS生产,炎症标志物,矩阵金属蛋白酶活性和细胞透.
- 研究的信号通路涉及血管光滑肌细胞 (VSMC) 中的环素A (CypA) 和Erk1/2酸化.
主要成果:
- 特定于内皮的Nox2过度表达导致Ang II介导的大动脉剖析在小鼠中,与野生类型对照不同.
- 诺克斯2转基因大动脉表现出增加的EC ROS,VCAM-1表达,MMP活性和炎症细胞透.
- ECs分泌了更多的CypA,这促进了VSMC Erk1/2酸化和ROS生产的增加,有助于大动脉剖析.
结论:
- 内皮细胞衍生的ROS在大动脉壁对AngII介导的大动脉剖析的敏感性中发挥着关键作用.
- ECs对ROS依赖的CypA分泌是一种关键的信号机制,它将EC ROS与大动脉壁结构损伤联系起来.
- 向EC ROS和CypA分泌可能为预防大动脉解剖提供新的治疗策略.
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