Lipolysis products from triglyceride-rich lipoproteins increase endothelial permeability, perturb zonula occludens-1 and F-actin, and induce apoptosis
Lipolysis products from triglyceride-rich lipoproteins increase endothelial permeability, perturb zonula occludens-1 and F-actin, and induce apoptosis
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DOI：
10.1152/ajpheart.00686.2006
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发表时间：
2007-06-01
影响因子：
4.8
通讯作者：
Rutledge, John C.
中科院分区：
文献类型：
--
作者：
Eiselein, Larissa;Wilson, Dennis W.;Rutledge, John C.
据报道，脂蛋白脂肪酶介导的富含磷脂酰肌醇的脂蛋白（TGRL）水解产生的产物可增加内皮层通透性。我们推测，这些增加的渗透性导致主动重排和溶解的连接屏障在人主动脉内皮细胞，以及诱导的凋亡级联。人主动脉内皮细胞用由人TGRL加脂蛋白脂肪酶共孵育产生的TGRL脂解产物处理。跨内皮电阻的测量表明，响应于TGRL脂解产物，内皮屏障功能的时间依赖性降低。免疫荧光定位的闭锁小带-1（ZO-1）显示放射状重排沿着细胞边界后1.5小时的脂解产物的治疗。通过罗丹明鬼笔环肽染色观察到F-肌动蛋白从细胞体到细胞边缘的同时重新分布。occludin和血管内皮钙粘蛋白的免疫荧光成像显示，这些蛋白重新定位，以及，虽然这些变化是不太突出的比ZO-1。暴露于脂解产物3小时的细胞的Western分析揭示ZO-1的片段化。闭合蛋白的减少。血管内皮钙粘蛋白无变化。脂解产物也增加caspase-3活性并诱导核碎裂。在孵育期间的任何时间点，处理均未引起细胞胀亡。这些结果表明TGRL脂解产物在内皮渗透性的文件调节中起重要作用。肌动蛋白细胞骨架的组织，连接蛋白，特别是ZO-1的定位和表达，以及细胞凋亡的诱导。
Products generated from lipoprotein lipase-mediated hydrolysis of triglyceride-rich lipoproteins (TGRL) are reported to increase endothelial layer permeability. We hypothesize that these increases in permeability result from the active rearrangement and dissolution of the junctional barrier in human aortic endothelial cells, as well as induction of the apoptotic cascade. Human aortic endothelial cells were treated with TGRL lipolysis products generated from coincubation of human TGRL plus lipoprotein lipase. measurement of transendothelial electrical resistance demonstrated a time-dependent decrease in endothelial barrier function in response to TGRL lipolysis products. Immunofluorescent localization of zonula occludens-1 (ZO-1) showed radial rearrangement along cell borders after 1.5 h of treatment with lipolysis products. A concurrent redistribution of F-actin from the cell body to the cell margins was observed via rhodamine phalloidin staining. Immunofluorescent imaging for occludin and vascular endothelial cadherin showed that these proteins relocalize as well, although these changes are less prominent than for ZO-1. Western analysis of cells exposed to lipolysis products for 3 h revealed the fragmentation of ZO-1. a reduction In occludin. and no change of vascular endothelial cadherin. Lipolysis products also increased caspase-3 activity and induced nuclear fragmentation. Treatments did not Cause oncosis in cells at any, point during the incubation. These results demonstrate that TGRL lipolysis products play an important role in file regulation of endothelial permeability. the organization of the actin cytoskeleton, the localization and expression of junctional proteins, especially ZO-1, and the induction of apoptosis.