氧化应激通过激活TLR2与新型内源性连接体来诱导血管生成
Xiaoxia Z West1, Nikolay L Malinin, Alona A Merkulova
1Department of Molecular Cardiology, J. J. Jacobs Center for Thrombosis and Vascular Biology, NB50, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
Nature
|October 8, 2010
概括
氧化应激产物,如碳基,通过激活托尔类受体2 (TLR2) 来触发新的血管生长 (血管生成). 这一发现将炎症,免疫力和血管形成与愈合和疾病联系在一起.
科学领域:
- 生物医学科学 生物医学科学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 炎症,氧化应激和新血管化在组织修复和癌症中相互关联.
- 低氧驱动的血管生成是可以理解的,但炎症诱导的氧化和新血管生长之间的联系尚不清楚.
研究的目的:
- 为了研究脂质氧化产品在炎症诱导的血管生成中的作用.
- 确定将氧化应激与血管形成联系起来的分子机制.
主要方法:
- 在衰老的组织和瘤中发现了已识别的 carboxyalkylpyrroles (例如, ω-(2-carboxyethyl) pyrrole - CEP).
- 在内皮细胞上研究了托尔类受体2 (TLR2) 对CEP的识别.
- 利用后肢缺血,伤口愈合和小鼠瘤模型.
- 评估了TLR2和MyD88信号在CEP诱导的血管生成和内皮细胞迁移中的作用.
主要成果:
- 包括CEP在内的carboxyalkylpyrroles在炎症和伤口愈合过程中产生,并在衰老的组织和瘤中积累.
- 通过MyD88依赖的TLR2信号传递,CEP可以独立于血管内皮生长因子 (VEGF) 诱导血管新生.
- 中和内源性碳酸基醇会影响伤口愈合,再血管化和瘤血管生成.
- TLR2和MyD88对于CEP刺激的Rac1激活和内皮细胞迁移至关重要.
结论:
- 确立了碳氧基烯醇作为关键介质,将氧化应激和血管生成联系起来.
- 识别了托尔类受体2 (TLR2) 作为一种用于氧化相关分子模式的新型传感器.
- 提供一个新的分子链接连接炎症,氧化应激,先天免疫力和血管生成.
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