瘤缩因子-α受体p75在缺血引起的新血管化中是必需的
David A Goukassian1, Gangjian Qin, Christine Dolan
1Division of Cardiovascular Diseases, Department of Medicine, Caritas St Elizabeth's Medical Center, Boston, Mass, USA. dgoukass@bu.edu
Circulation
|January 31, 2007
概括
p75 TNF受体对于缺血后的血管修复至关重要,特别是在老年人中. 准这种受体可能会改善血管疾病的恢复.
科学领域:
- 心血管生物学 心血管生物学
- 免疫学 免疫学 免疫学
- 再生医学是一种再生医学.
背景情况:
- 老龄化增加了外围动脉疾病的风险.
- 瘤坏死因子-α (TNF-α) 影响缺血组织中的血管生成.
- 在血管生成中TNF-α受体 (TNFR1/p55,TNFR2/p75) 的作用尚不清楚.
研究的目的:
- 研究TNFR2/p75在新血管化和后肢缺血的恢复中的作用.
- 确定TNFR2/p75功能在血管修复中是否依赖年龄.
- 识别潜在的治疗目标,以改善后缺血性恢复.
主要方法:
- 在年轻和老的TNFR2/p75淘汰赛 (p75KO) 和野生型小鼠中使用后肢缺血模型.
- 评估肢体存活率,血液流动,毛细血管密度和血管生成因子 (VEGF,FGF-2) 的表达.
- 评估了骨髓移植对p75KO小鼠肢体恢复的影响.
主要成果:
- 旧的p75KO小鼠表现出100%的四肢自动截肢,与野生类型对照不同.
- p75KO小鼠表现出血流受损,内皮细胞亡增加,毛细血管密度降低.
- 在p75KO小鼠中,VEGF和FGF-2表达和循环内皮原生细胞显著降低.
- 骨髓移植可以防止老p75KO小鼠失去四肢.
结论:
- 缺血后的新血管化部分依赖于骨髓衍生细胞中的p75 TNF受体信号传递.
- TNFR2/p75信号传递对于内皮细胞存活,生长因子表达,祖细胞调动和分化以及附带血管发育至关重要.
- TNFR2/p75成为后缺血性恢复的年龄相关限制,为血管疾病提供潜在的治疗点.
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