内皮PTP1B删除促进VWF外细胞和静脉血栓炎症
Konstantinos Zifkos1, Magdalena L Bochenek1,2, Rajinikanth Gogiraju2
1Center for Thrombosis and Hemostasis (K.Z., M.L.B., D.P., K.K., W.R., C.R.), University Medical Center Mainz, Germany.
Circulation research
|April 2, 2024
概括
从内皮细胞中去除蛋白氨酸酸酶1B (PTP1B) 会促进静脉血栓炎症. 这是通过增加VWF外细胞和中性粒细胞的招募而发生的,导致更大的血栓.
科学领域:
- 血管生物学 血管生物学
- 免疫学 免疫学 免疫学
- 血栓形成的原因是血栓形成.
背景情况:
- 内皮细胞激活释放出促凝的细胞外囊泡和炎症媒介.
- 内皮膜外细胞分裂是通过酸化来调节的.
- 蛋白质氨酸酸酶1B (PTP1B) 脱酸化了参与外细胞分裂的蛋白质.
研究的目的:
- 为了研究内皮PTP1B在静脉血栓炎症中的作用.
- 为了确定PTP1B缺乏是否促进内皮细胞外和血栓形成.
主要方法:
- 有PTP1B (End.PTP1B-KO) 诱导性内皮缺失的小鼠经历了下静脉结.
- 主要内皮细胞和人静脉内皮细胞被用于机械学研究.
- 血管超声波,组织学和静脉内显微镜评估了血栓形成和中性粒细胞的招募.
主要成果:
- 末期PTP1B-KO小鼠表现出较大的静脉血栓与增加的中性粒细胞透.
- 缺乏PTP1B的内皮细胞表现出粘附分子 (CD62P,VWF) 的增强表达和细胞外囊释放的增加.
- 中性粒细胞粘附是由VWF调解,并通过NF-κB抑制被阻止.
- 减少了SNAP23的PTP1B结合和氨酸脱化,导致VWF表细胞分裂的增加.
结论:
- 内皮PTP1B的删除促进静脉血栓炎症.
- 这是通过增强的SNAP23酸化,VWF外细胞分裂和中性粒细胞招募来调解的.
- 抑制NF-κB信号传递可以恢复正常功能.
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