The Angiopoietin-Tie2 Pathway in Critical Illness.
The Angiopoietin-Tie2 Pathway in Critical Illness.
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DOI：
10.1016/j.ccc.2019.12.003
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发表时间：
2020-04
影响因子：
4.3
通讯作者：
Parikh SM
中科院分区：
文献类型：
--
作者：
Sack KD;Kellum JA;Parikh SM
脓毒症和急性呼吸窘迫综合征（ARDS）的致命特征与小血管的健康有关。例如，蛋白质液体对肺泡的浸润通常是由微血管屏障的破坏引起的。发炎的微血管内自发形成血栓会加剧器官缺血，并在最后阶段爆发为明显的弥散性血管内凝血（DIC）。血管内皮中的信号轴，即血管生成素-Tie2 通路，可能在从微血管完整性到病理破坏的突然转变中发挥核心作用。当血管处于静止状态时，Tie2 信号传导高度活跃：稳定连接、抗炎和抗凝血。然而，在炎症过程中，Tie2 信号传导会随着其内源性拮抗剂 Angiopoietin-2 的水平上升 1-2 个数量级而迅速关闭。当 Tie2 信号减弱时，微血管屏障崩溃，内皮细胞与白细胞粘附，血管壁不再阻止自发凝血。本综述将总结大量临床前和临床结果，这些结果表明 Tie2 通路与脓毒症和 ARDS 的发病机制有关。来自世界各地的研究小组的结果现在将血管生成素确定为脉管系统的动态循环标志物。此外，Tie2 正在成为恢复脓毒症和急性呼吸窘迫综合征（ARDS）微血管健康的有前景的靶点。对 Tie2 通路的转化探索可能会促进危重患者的诊断、监测和治疗方式的进步。
Lethal features of sepsis and acute respiratory distress syndrome (ARDS) relate to the health of small blood vessels. For example, infiltration of the alveoli with proteinaceous fluid is often driven by breach of the microvascular barrier. Spontaneous thrombus formation within inflamed microvessels exacerbates organ ischemia, and in its final stages, erupts into overt disseminated intravascular coagulation (DIC). A signaling axis in the vascular endothelium, the Angiopoietin-Tie2 pathway, may play a central role in the abrupt transition from microvascular integrity to pathological disruption. Tie2 signaling is highly active when vessels are in their quiescent state: stable junctions, anti-inflammatory, and anti-coagulant. During inflammation however, Tie2 signaling is rapidly toggled off as levels of its endogenous antagonist, Angiopoietin-2, rise by 1–2 orders of magnitude. When Tie2 signaling drops, the microvascular barrier collapses, endothelium becomes adhesive to leukocytes, and the vessel wall no longer prevents spontaneous coagulation. This review will summarize a large body of preclinical and clinical results that implicate the Tie2 pathway in the pathogenesis of sepsis and ARDS. Results from groups worldwide now identify Angiopoietins as dynamic circulating markers of the vasculature. Furthermore, Tie2 is emerging as a promising target to restore microvascular health in sepsis and ARDS. Translational pursuit of the Tie2 pathway may enable advances in the way critically ill patients are diagnosed, monitored, and treated.
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影响因子：
8.8
作者：
David S;Mukherjee A;Ghosh CC;Yano M;Khankin EV;Wenger JB;Karumanchi SA;Shapiro NI;Parikh SM
通讯作者：
Parikh SM
影响因子：
11.8
作者：
Gale, NW;Thurston, G;Yancopoulos, GD
通讯作者：
Yancopoulos, GD
DOI：
10.1038/nsb880
发表时间：
2003-01-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Davis, S;Papadopoulos, N;Yancopoulos, GD
通讯作者：
Yancopoulos, GD
DOI：
10.1164/rccm.200109-016oc
发表时间：
2002-07-01
影响因子：
24.7
作者：
De Backer, D;Creteur, J;Vincent, JL
通讯作者：
Vincent, JL
影响因子：
13.7
作者：
Campochiaro, Peter A.;Sophie, Raafay;Peters, Kevin
通讯作者：
Peters, Kevin