Soluble Vascular Endothelial-Cadherin Levels in Patients With Sepsis Treated With Direct Hemoperfusion With a Polymyxin B-immobilized Fiber Column
Soluble Vascular Endothelial-Cadherin Levels in Patients With Sepsis Treated With Direct Hemoperfusion With a Polymyxin B-immobilized Fiber Column
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DOI：
10.1111/1744-9987.12215
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发表时间：
2014-06-01
影响因子：
1.9
通讯作者：
Kobayashi, Masaki
中科院分区：
文献类型：
--
作者：
Ebihara, Itaru;Hirayama, Kouichi;Kobayashi, Masaki
毛细血管通透性是所有器官床微循环的一个严格调节的特征；然而，在脓毒症中，这一特征从根本上改变了。一些分子被认为是毛细血管通透性和血管内皮细胞钙粘附素内化的相关因素，通过血管内皮生长因子受体诱导的信号转导导致血管内皮细胞脱离和跨内皮通透性增加。我们研究了败血症患者血清中可溶性VE-钙粘附素的水平。采用酶联免疫法测定了47例脓毒症患者经多粘菌素B固定纤维柱(DHP-PMX)直接血液灌流治疗后血清中可溶性VE-钙粘附素的水平。脓毒症患者PMX-DHP治疗前血清可溶性VE-钙粘附素水平为3424.1+/-2033.0 ng/mL，明显低于对照组(5862.0+/-1521.2 ng/mL；P<；0.0001)。PMX-DHP治疗前后血清可溶性VE-钙粘附素水平无明显变化。PMX-DHP治疗前存活组与死亡组间血清可溶性VE-钙粘附素水平无显著差异，PMX-DHP治疗后各时间点两组间血清sVE-cadherin水平亦无显著差异。除白细胞计数外，血清VE-钙粘附素水平与临床指标无相关性(r=-0.277，P=0.0009)。VE-钙粘蛋白水平与血管生成素1、2水平无相关性。综上所述，脓毒症患者VE-钙粘蛋白水平与毛细血管通透性之间的关系尚不明确。可溶性VE-钙粘蛋白不能反映细胞间连接可塑性和完整性之间的平衡，但通过其磷酸化或内化来稳定VE-钙粘蛋白可能与毛细血管通透性有关。
Capillary permeability is a tightly regulated feature of microcirculation in all organ beds; however, in sepsis this feature is fundamentally altered. Several molecules are investigated as associated factors with capillary permeability and vascular endothelial (VE)-cadherin internalization by vascular endothelial growth factor (VEGF)induced signaling through VEGF receptors leads to increased vascular endothelial cell detachment and transendothelial permeability. We investigated serum soluble VE-cadherin levels in septic patients. An enzyme-linked immunoassay was used to measure serum soluble VE-cadherin levels in 47 septic patients treated by direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX). The serum soluble VE-cadherin level of septic patients before PMX-DHP was 3424.1 +/- 2033.0 ng/mL, which was significantly lower than that of the controls (5862.0 +/- 1521.2 ng/mL; P < 0.0001). The time course of serum soluble VE-cadherin levels remained unchanged during PMX-DHP therapy. There was no significant difference in serum soluble VE-cadherin levels before PMX-DHP therapy between survivors and non-survivors, and there was no significant difference in those levels between the groups at any time after the initiation of PMX-DHP therapy. There was no correlation between soluble VE-cadherin levels and clinical data, except white blood cell count (r = -0.277, P = 0.0009). There was no correlation between soluble VE-cadherin levels and the levels of angiopoietin 1 and 2. In summary, the relationship between VE-cadherin and capillary permeability in sepsis could not be demonstrated. Soluble VE-cadherins are not reflected in the balance between intercellular junction plasticity and integrity, but VE-cadherin stabilization by its phosphorylation or internalization may be associated with capillary permeability.