Angiogenic factors in sepsis: are we ready for the new therapeutic era?
Angiogenic factors in sepsis: are we ready for the new therapeutic era?
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脓毒症中的血管生成因素：我们准备好迎接新的治疗时代了吗？
DOI：
10.1186/cc13710
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发表时间：
2014-01
期刊：
影响因子：
15.1
通讯作者：
Yao-Qing Tang
中科院分区：
文献类型：
--
作者：
Ru-Yuan Zhang;Hong Zhang;Jie Huang;Hong-Ping Qu;Yao-Qing Tang
最近，Fiusa和他的同事[1]描述了高血管生成素(Ang)-2/Ang-1比率与发热性中性粒细胞减少症患者感染性休克的高风险相关。虽然这项研究未能检测到两组结果之间的血管内皮生长因子(VEGF)水平有统计学意义的差异，但败血症休克患者发热性中性粒细胞减少亚组中观察到的Ang-2浓度和Ang-2/Ang-1比值的增加表明，血管生成因子可能是败血症有希望的治疗靶点。血管生成因子及其受体(包括Ang/Tie2和VEGF/VEGF受体通路)的失衡已被证明预测败血症患者的不良预后，并被认为是多器官功能障碍的一个促成因素。由于这些原因，针对Ang/Tie2和VEGF/VEGF受体的几种策略正在临床前脓毒症模型中探索；然而，这些药物大多不能用于临床实践或不适用于临床实践。开发以血管生成为靶点的抗癌药物的努力已导致血管内皮生长因子及其受体的抑制剂获得批准，特别是贝伐单抗。正如最近在重症监护中报道的那样，贝伐单抗已被证明在动物模型中治疗败血症有效[2]。目前的研究巩固和扩展了先前的发现，即在脓毒症状态下Ang-2水平升高，并已被确立为识别死亡率最高的患者组的预后生物标志物。有趣的是，最近通过使用Ang-2抗体治疗，Ziegler和他的同事[3]表明抑制Ang-2对脓毒症小鼠的存活有显著影响。AMG 386是一种正在研究中的多肽-Fc融合蛋白，它通过阻止血管生成的相互作用来抑制血管生成
Recently, Fiusa and colleagues [1] described that a high angiopoietin (Ang)-2/Ang-1 ratio is associated with a high risk of septic shock in patients with febrile neutropenia. Although this study failed to detect a statistically significant difference in the levels of vascular endothelial growth factor (VEGF) between both outcome groups, the observed increased Ang-2 concentrations and Ang-2/Ang-1 ratio in the febrile neutropenia subgroup of patients with septic shock address the concept that angiogenic factors could be a promising therapeutic target in sepsis.The imbalance of angiogenic factors and their receptors, including the Ang/Tie2 and VEGF/VEGF receptor pathways, has been shown to predict poor prognosis in sepsis and has been implicated as a contributing factor in multiple organ dysfunction. For these reasons, several strategies targeting Ang/Tie2 and VEGF/VEGF receptor are being explored in preclinical sepsis models; however, most of these agents are unavailable or not applicable in clinical practice. Efforts to develop anticancer agents that target angiogenesis have led to the approval of inhibitors of VEGF and its receptor, specifically bevacizumab. As recently reported in Critical Care, bevacizumab has proven effective in the treatment of sepsis in an animal model [2]. The current study reinforces and extends previous findings that Ang-2 levels are increased in the septic state and have been established as a prognostic biomarker for identification of the patient group with the highest mortality rates. Interestingly, most recently by using Ang-2 antibody treatment, Ziegler and colleagues [3] showed that inhibition of Ang-2 has a significant effect on survival of mice with sepsis. AMG 386 is an investigational peptide-Fc fusion protein that inhibits angiogenesis by preventing the interaction of
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DOI：
10.1186/cc12848
发表时间：
2013-08-05
期刊：
Critical care (London, England)
影响因子：
--
作者：
Luz Fiusa MM;Costa-Lima C;de Souza GR;Vigorito AC;Penteado Aranha FJ;Lorand-Metze I;Annichino-Bizzacchi JM;de Souza CA;De Paula EV
通讯作者：
De Paula EV
影响因子：
10.7
作者：
通讯作者：
--
影响因子：
45.3
作者：
Herbst, Roy S.;Hong, David;Rosen, Lee S.
通讯作者：
Rosen, Lee S.
DOI：
10.1186/cc12742
发表时间：
2013-05-27
期刊：
Critical care (London, England)
影响因子：
--
作者：
Jeong SJ;Han SH;Kim CO;Choi JY;Kim JM
通讯作者：
Kim JM
影响因子：
15.9
作者：
Ziegler, Tilman;Horstkotte, Jan;Kupatt, Christian
通讯作者：
Kupatt, Christian