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A tale of two ligands: angiopoietins, the endothelium, and outcomes

机译:关于两个配体的故事:血管生成素,内皮和结果

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Angiopoietins signal via the Tie-2 receptor and are essential molecules for vasculogenesis during development and in the adult state play roles in vascular stability as well as inflammation and appear to be involved in the dysregulation of the endothelium in illness. Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) are, respectively, agonists and competitive partial agonists, which have been found to undergo alterations in individuals with sepsis. In sepsis, Ang-2 levels are elevated and Ang-1 is decreased. In the previous issue of Critical Care, Fiusa and colleagues measure circulating Ang-1 and Ang-2 along with other growth factors in humans with febrile neutropenia. The authors found that an increased Ang-2/Ang-1 ratio, or an elevated Ang-2 level, at the time of an initial fever, is associated with subsequent development of septic shock and death. These findings validate that the Ang-2/Ang-1 balance, which is thought to reflect overall signaling via the Tie-2 receptor, is relevant to outcomes in patients with sepsis. Importantly, the specimens were obtained far in advance of the development of septic shock, suggesting that detectable alterations in this pathway may provide early clues regarding outcomes. This study adds to the evidence that angiopoietins are early markers of endothelial dysfunction in sepsis and provide prognostic information regarding outcomes.
机译:血管生成素通过Tie-2受体发出信号,是发育过程中血管生成所必需的分子,在成年状态中,血管生成素在血管稳定性以及炎症中发挥作用,并且似乎与疾病中的内皮失调有关。血管生成素-1(Ang-1)和血管生成素2(Ang-2)分别是激动剂和竞争性部分激动剂,已经发现败血症患者会发生改变。在败血症中,Ang-2水平升高而Ang-1水平降低。在上一期的《重症监护》中,Fiusa及其同事测量了发热性中性粒细胞减少症患者的循环Ang-1和Ang-2以及其他生长因子。作者发现,初次发烧时,Ang-2 / Ang-1比值升高或Ang-2水平升高与败血性休克和死亡的发展有关。这些发现证实,Ang-2 / Ang-1平衡被认为反映了通过Tie-2受体的总体信号传导,与败血症患者的预后有关。重要的是,标本是在感染性休克发生之前就获得的,这表明该途径中可检测到的改变可能会提供有关预后的早期线索。这项研究增加了证据,即血管生成素是败血症中内皮功能障碍的早期标志物,并提供有关预后的预后信息。

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