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血管新生素受体Tie2在动脉内皮中具有甲状腺保护作用
Andrey Anisimov1,2, Shentong Fang1,2,3, Karthik Amudhala Hemanthakumar1,2
1Wihuri Research Institute, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
Nature cardiovascular research
|July 21, 2023
概括
与Tie1.1不同,Tie2受体可以防止动脉样硬化. 遗传证据表明,Tie2缺乏通过增加动脉中的炎症和免疫细胞积累来促进这种疾病.
科学领域:
- 心血管生物学 心血管生物学
- 分子医学是分子医学.
- 免疫学 免疫学 免疫学
背景情况:
- 动脉样硬化涉及白细胞和动脉壁中的常驻细胞,特别是在血液流动受到干扰的地方.
- 内皮Tie1受体氨酸激酶表达在受损的流动部位上增加,其减少减少动脉样硬化和炎症.
- 在动脉样硬化中Tie2氨酸激酶的作用尚不清楚.
研究的目的:
- 在动脉样硬化背景下研究Tie2氨酸激酶的功能.
- 为了确定Tie2是否在冠状动脉疾病中起着保护性或有害的作用.
主要方法:
- 在人类受试者的遗传分析和动脉样硬化小鼠模型.
- 对Tie2和Tie1的内皮特异性基因删除.
- 评估Foxo1局部化,粘附分子表达和免疫细胞透.
- 对大动脉纤维细胞中Tie2表达的分析及其对炎症相关基因的影响.
主要成果:
- 来自人类和小鼠的遗传证据将TIE2与对冠状动脉疾病的保护联系起来.
- 在动脉内皮中删除Tie2 (或Tie1和Tie2两者) 会加剧动脉样硬化.
- 这种恶化是由增加的Foxo1核定位,内皮粘附分子表达和免疫细胞积累的介导.
- 大动脉纤维细胞中的Tie2沉默增加了与炎症相关的基因表达.
结论:
- Tie2受体作为主要的内皮血管蛋白受体,提供对动脉样硬化的保护.
- 与Tie1不同,Tie2在预防这种心血管疾病的发展方面发挥着主要的保护作用.
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