Involvement of ROCK-mediated endothelial tension development in neutrophil-stimulated microvascular leakage
Involvement of ROCK-mediated endothelial tension development in neutrophil-stimulated microvascular leakage
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DOI：
10.1152/ajpheart.00238.2005
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发表时间：
2006-02-01
影响因子：
4.8
通讯作者：
Yuan, SY
中科院分区：
文献类型：
--
作者：
Breslin, JW;Sun, HR;Yuan, SY
中性粒细胞刺激的微血管渗漏中rock介导的内皮张力发展的参与。[J]中华心血管病杂志，2016,31(2):444 - 444。2005年9月19日首次出版；doi: 10.1152 / ajpheart.00238.2005。中性粒细胞引起的冠状动脉微血管屏障功能障碍是心脏病的重要病理生理事件。目前，中性粒细胞诱导的微血管渗漏的确切细胞和分子机制尚不清楚。本研究的目的是验证rho激酶（ROCK）增加冠状静脉通透性与内皮张力升高相关的假设。我们评估了分离的猪冠状静脉和冠状静脉内皮细胞（CVEC）单层对白蛋白（P-a）的通透性。通过测量CVEC单层膜的跨内皮电阻（TER）来评估内皮屏障功能。同时，我们测量了在胶原凝胶上生长的cvec的等长张力。组成活性(ca)-ROCK蛋白转移到分离的冠状动脉小静脉或CVEC单层引起CVEC中P-a的显著增加和TER的降低。ROCK抑制剂Y-27632阻断了ca-ROCK诱导的变化。c5a激活的中性粒细胞（10(6)/ml）也显著升高静脉P-a， Y-27632和结构不同的ROCK抑制剂H-1152对P-a有剂量依赖性抑制。在CVEC单层中，活化的中性粒细胞随着等距张力的升高而增加渗透性，Y-27632或H-1152抑制了这两种作用。ca-ROCK处理也显著增加CVEC单层通透性和等长张力，并伴有肌动蛋白聚合和肌球蛋白调节轻链Thr18/Ser19磷酸化升高。数据表明，在中性粒细胞活化过程中，ROCK促进微血管渗漏，与肌动蛋白-肌球蛋白介导的内皮细胞紧张发展有关。
Involvement of ROCK-mediated endothelial tension development in neutrophil-stimulated microvascular leakage. Am J Physiol Heart Circ Physiol 290: H741-H750, 2006. First published September 19, 2005; doi:10.1152/ajpheart.00238.2005.-Neutrophil-induced coronary microvascular barrier dysfunction is an important pathophysiological event in heart disease. Currently, the precise cellular and molecular mechanisms of neutrophil-induced microvascular leakage are not clear. The aim of this study was to test the hypothesis that rho kinase (ROCK) increases coronary venular permeability in association with elevated endothelial tension. We assessed permeability to albumin (P-a) in isolated porcine coronary venules and in coronary venular endothelial cell (CVEC) monolayers. Endothelial barrier function was also evaluated by measuring transendothelial electrical resistance (TER) of CVEC monolayers. In parallel, we measured isometric tension of CVECs grown on collagen gels. Transference of constitutively active (ca)-ROCK protein into isolated coronary venules or CVEC monolayers caused a significant increase in P-a and decreased TER in CVECs. The ROCK inhibitor Y-27632 blocked the ca-ROCK-induced changes. C5a-activated neutrophils (10(6)/ml) also significantly elevated venular P-a, which was dose-dependently inhibited by Y-27632 and a structurally distinct ROCK inhibitor, H-1152. In CVEC monolayers, activated neutrophils increased permeability with a concomitant elevation in isometric tension, both of which were inhibited by Y-27632 or H-1152. Treatment with ca-ROCK also significantly increased CVEC monolayer permeability and isometric tension, coupled with actin polymerization and elevated phosphorylation of myosin regulatory light chain on Thr18/Ser19. The data suggest that during neutrophil activation, ROCK promotes microvascular leakage in association with actin-myosin-mediated tension development in endothelial cells.