Angiopoietins and Tie2 in vascular inflammation.
Angiopoietins and Tie2 in vascular inflammation.
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血管炎的血管蛋白和TIE2在血管炎症中。
DOI：
10.1097/moh.0000000000000361
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发表时间：
2017-09
影响因子：
3.2
通讯作者：
Parikh SM
中科院分区：
文献类型：
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作者：
Parikh SM
作为对严重感染的机体反应的一个子集，宿主血管反应近年来受到越来越多的关注。小血管为促进病原体清除而进行的转变，如果发生范围太广或持续时间太长，可能会对宿主有害。血管渗漏和发炎的不良临床表现包括损害关键器官功能的水肿和循环休克。表明这种宿主血管反应可能是可测量的并且可能是可靶向的。 Tie2 是一种在血管内皮中大量富集的受体酪氨酸激酶，其强直信号可积极维持血管静止。当 Tie2 失活时，内皮细胞中会释放重要的分子制动器，进而加剧炎症和血管渗漏。 Tie2 的配体 Angiopoietin-1 和 -2 调节其激活状态。对数千名人类受试者进行的遗传和分子研究将 Tie2 和血管生成素失衡与细菌性败血症、其他严重感染甚至急性无菌性炎症引起的主要不良临床事件联系起来。 Tie2 信号轴可能构成全身炎症中的分子开关，可以测量和操纵该开关以治疗靶标宿主血管反应。
As a subset of the organism-wide reaction to severe infection, the host vascular response has received increasing attention in recent years. The transformation that small blood vessels undergo to facilitate the clearance of pathogens may become harmful to the host if it occurs too broadly or if it is sustained too long. Adverse clinical manifestations of leaky and inflamed blood vessels include edema impairing the function of critical organs and circulatory shock. suggest that this host vascular response may be both measurable and potentially targetable. Tie2 is a receptor tyrosine kinase heavily enriched in the vascular endothelium whose tonic signaling actively maintains vascular quiescence. When Tie2 becomes inactivated, important molecular brakes are released in the endothelium that in turn, potentiate inflammation and vascular leakage. The ligands of Tie2, Angiopoietin-1 and -2, regulate its activation status. Genetic and molecular studies spanning thousands of human subjects link Tie2 and imbalance of the Angiopoietins to major adverse clinical events arising from bacterial sepsis, other severe infections, and even acute sterile inflammation. The Tie2 signaling axis may constitute a molecular switch in systemic inflammation that can be measured and manipulated to target the host vascular response therapeutically.