von Willebrand factor enhances microvesicle-induced vascular leakage and coagulopathy in mice with traumatic brain injury.
von Willebrand factor enhances microvesicle-induced vascular leakage and coagulopathy in mice with traumatic brain injury.
复制标题
冯维勒布兰德因子增强脑外伤小鼠中微泡诱导的血管渗漏和凝血病。
DOI：
10.1182/blood-2018-03-841932
复制
发表时间：
2018-09
期刊：
影响因子：
20.3
通讯作者：
Dong Jing-Fei
中科院分区：
文献类型：
--
作者：
Wu Yingang;Liu Wei;Zhou Yuan;Hilton Tristan;Zhao Zilong;Liu Wei;Wang Min;Yeon Jason;Houck Katie;Thiagarajan Perumal;Zhang Fangyi;Shi Fu-Dong;Wu Xiaoping;Li Min;Zhang Jianning;Dong Jing-Fei
血管性血友病因子（VWF）是一种粘附配体，其活性受金属蛋白酶ADAMTS-13（一种具有血小板反应蛋白1型重复13的崩解素和金属蛋白酶）的蛋白水解调节。血浆VWF水平升高被广泛认为是创伤和炎症中内皮细胞活化的标志，但其在这些病理条件中的因果作用仍不明确。通过液体冲击损伤小鼠模型，我们证明了急性创伤性脑损伤（TBI）期间释放的VWF被激活并成为微泡结合。vwf结合的微泡促进血管渗漏和全身凝血。在脑外伤前后给予重组ADAMTS-13可降低VWF的反应性，但对VWF分泌的影响最小。rADAMTS-13保护内皮细胞屏障的完整性，并通过增强VWF切割而不损害基础止血来预防tbi诱导的凝血功能障碍。乳酸粘附素促进微泡清除的效果与rADAMTS-13相似。本研究揭示了VWF和细胞微泡在tbi诱导的血管渗漏和凝血病中的一种新的协同作用，并证明了rADAMTS-13的保护作用。
von Willebrand factor (VWF) is an adhesive ligand, and its activity is proteolytically regulated by the metalloprotease ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type 1 repeat 13). An elevated level of plasma VWF has been widely considered a marker for endothelial cell activation in trauma and inflammation, but its causal role in these pathological conditions remains poorly defined. Using a fluid percussion injury mouse model, we demonstrated that VWF released during acute traumatic brain injury (TBI) was activated and became microvesicle-bound. The VWF-bound microvesicles promoted vascular leakage and systemic coagulation. Recombinant ADAMTS-13 given either before or after TBI reduced the VWF reactivity with minimal influence on VWF secretion. rADAMTS-13 protected the integrity of endothelial cell barriers and prevented TBI-induced coagulopathy by enhancing VWF cleavage without impairing basal hemostasis. Promoting microvesicle clearance by lactadherin had efficacy similar to that of rADAMTS-13. This study uncovers a novel synergistic action between VWF and cellular microvesicles in TBI-induced vascular leakage and coagulopathy and demonstrates protective effects of rADAMTS-13.
登录
查看更多内容
乳粘素促进微泡清除以预防凝血障碍并提高严重 TBI 小鼠的存活率
影响因子：
20.3
作者：
Zhou Yuan;Cai Wei;Zhao Zilong;Hilton Tristan;Wang Min;Yeon Jason;Liu Wei;Zhang Fangyi;Shi Fu-Dong;Wu Xiaoping;Thiagarajan Perumal;Li Min;Zhang Jianning;Dong Jing-fei
通讯作者：
Dong Jing-fei
影响因子：
20.3
作者：
Zilong Zhao;Min Wang;Ye Tian;Tristan Hilton;Breia J. Salsbery;E. Z. Zhou;Xiaoping Wu;P. Thiagarajan;É. Boilard;Min Li;Jian-ning Zhang;Jing-fei Dong
通讯作者：
Zilong Zhao;Min Wang;Ye Tian;Tristan Hilton;Breia J. Salsbery;E. Z. Zhou;Xiaoping Wu;P. Thiagarajan;É. Boilard;Min Li;Jian-ning Zhang;Jing-fei Dong
VEGI 通过抑制实验性脑外伤中的 TLR4/NF-κ B 信号通路来减轻炎症损伤和血脑屏障破坏
影响因子：
2.9
作者：
Gao, Weiwei;Zhao, Zilong;Zhang, Jianning
通讯作者：
Zhang, Jianning
影响因子：
4.2
作者：
Lu, DY;Mahmood, A;Chopp, M
通讯作者：
Chopp, M
影响因子：
13.5
作者：
Wu, Xin;Reddy, Doodipala Samba
通讯作者：
Reddy, Doodipala Samba