Angiopoietin-2 is a potential mediator of endothelial barrier dysfunction following cardiopulmonary bypass.
Angiopoietin-2 is a potential mediator of endothelial barrier dysfunction following cardiopulmonary bypass.
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DOI：
10.1016/j.cyto.2012.04.002
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发表时间：
2012-11
期刊：
影响因子：
3.8
通讯作者：
Kuempers, Philipp
中科院分区：
文献类型：
--
作者：
Clajus, Christian;Lukasz, Alexander;David, Sascha;Hertel, Barbara;Lichtinghagen, Ralf;Parikh, Samir M.;Simon, Andre;Ismail, Issam;Haller, Hermann;Kuempers, Philipp
内皮激活导致血管屏障功能障碍和器官衰竭是体外循环（CPB）心血管手术公认的并发症。内皮特异性血管生成素-Tie2配体-受体系统已被确定为内皮激活的非冗余调节因子。血管生成素-2 (Ang-2) 与 Tie2 受体的结合会拮抗 Tie2 信号传导，并使内皮屏障对促炎细胞因子产生反应。我们的目的是研究 CPB 后 Ang-2 释放的时间过程和潜在触发因素，以及 Ang-2 变化与血管通透性增加、器官功能障碍和结局的替代指标的关系。通过内部免疫发光测定 (ILMA) 测量 25 名成年患者（140 名筛查者）在 CPB 手术前和术后 0、12 和 24 小时的血清 Ang-2 水平，并与器官功能障碍、机械通气持续时间 (MV)、重症监护病房 (ICU) 住院时间 (LOS) 和医院死亡率等指标进行比较。通过将高 Ang-2 患者血清与内皮细胞 (EC) 一起孵育，在体外研究了 Ang-2 的作用。 CPB 后 Ang-2 水平从 0 小时时的 2.6 ± 2.4 ng/mL 稳定增加至 24 小时时的 7.3 ± 4.6 ng/mL (P < 0.001)。 Ang-2 的释放与 CPB 持续时间、主动脉交叉钳夹时间和 CPB 后乳酸水平相关。随访期间 Ang-2 的变化与动脉血氧分压 (PaO2)/吸入氧分数 (FiO2) 比率、肺泡-动脉氧张力差 (AaDO2)、血流动力学、体液平衡和疾病严重程度指标相关。 12 小时时的 Ang-2 水平可预测 MV 持续时间、ICU-LOS 和医院死亡率。高 Ang-2 患者血清在体外破坏了 EC 结构，用竞争性 Tie2 配体血管生成素-1 (Ang-1) 治疗可逆转这种效应。总的来说，我们的结果表明 Ang-2 是 CPB 后内皮屏障功能障碍的假定介质。这些发现表明，针对 Ang/Tie2 通路可能会减轻器官功能障碍并改善接受 CPB 的患者的预后。
Endothelial activation leading to vascular barrier dysfunction and organ failure is a well-recognized complication of cardiovascular surgery with cardiopulmonary bypass (CPB). The endothelial-specific angiopoietin–Tie2 ligand–receptor system has been identified as a non-redundant regulator of endothelial activation. Binding of angiopoietin-2 (Ang-2) to the Tie2 receptor antagonizes Tie2 signaling and renders the endothelial barrier responsive to pro-inflammatory cytokines. We aimed to study the time course and potential triggering factors of Ang-2 release after CPB, as well as the association of Ang-2 changes with surrogates of increased vascular permeability, organ dysfunction, and outcome. Serum levels of Ang-2 from 25 adult patients (140 screened) were measured before and at 0, 12, and 24 h following CPB procedure by in-house immuno-luminometric assay (ILMA), and compared with indices of organ dysfunction, duration of mechanical ventilation (MV), length of stay (LOS) in the intensive care unit (ICU), and hospital mortality. The effect of Ang-2 was studied in vitro by incubating high Ang-2 patient serum with endothelial cells (EC). Ang-2 levels steadily increased from 2.6 ± 2.4 ng/mL at 0 h up to 7.3 ± 4.6 ng/mL at 24 h following CPB (P < 0.001). The release of Ang-2 correlated with the duration of CPB, aortic cross-clamp time, and post-CPB lactate levels. Changes in Ang-2 during follow-up correlated with partial pressure of oxygen in arterial blood (PaO2)/fraction of inspired oxygen (FiO2) ratio, alveolar–arterial oxygen tension difference (AaDO2), hemodynamics, fluid balance, and disease severity measures. Ang-2 levels at 12 h predicted the duration of MV, ICU-LOS, and hospital mortality. High Ang-2 patient sera disrupted EC architecture in vitro, an effect reversed by treatment with the competitive Tie2 ligand angiopoietin-1 (Ang-1). Collectively, our results suggest that Ang-2 is a putative mediator of endothelial barrier dysfunction after CPB. These findings suggest that targeting the Ang/Tie2 pathway may mitigate organ dysfunction and improve outcome in patients undergoing CPB.
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影响因子：
15.1
作者：
Kuempers, Philipp;Gueler, Faikah;Shushakova, Nelli
通讯作者：
Shushakova, Nelli
影响因子：
8.8
作者：
Huang, Yao Qi;Sauthoff, Harald;Hay, John G.
通讯作者：
Hay, John G.
DOI：
10.1186/cc7866
发表时间：
2009
期刊：
Critical care (London, England)
影响因子：
--
作者：
Kümpers P;van Meurs M;David S;Molema G;Bijzet J;Lukasz A;Biertz F;Haller H;Zijlstra JG
通讯作者：
Zijlstra JG
影响因子：
120.7
作者：
LEGALL, JR;LEMESHOW, S;SAULNIER, F
通讯作者：
SAULNIER, F
影响因子：
38.9
作者：
Kuempers, Philipp;Hafer, Carsten;Faulhaber-Walter, Robert
通讯作者：
Faulhaber-Walter, Robert