Angiopoietin-1 decreases plasma leakage by reducing number and size of endothelial gaps in venules
Angiopoietin-1 decreases plasma leakage by reducing number and size of endothelial gaps in venules
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DOI：
10.1152/ajpheart.00542.2005
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发表时间：
2006-01-01
影响因子：
4.8
通讯作者：
McDonald, DM
中科院分区：
文献类型：
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作者：
Baffert, F;Le, T;McDonald, DM
血管生成素-1（Angiopoietin-1，Ang-1）在胚胎发育过程中对原始血管丛的重塑和壁细胞的募集至关重要。在成人血管系统中，Ang-1可以减少炎症中的血浆渗漏，但这种作用的机制尚不清楚。在本研究中，我们确定了Ang-1在小鼠气道中的抗渗漏作用的大小和细胞机制。静脉注射缓激肽导致荧光微球（直径25 - 1，000 nm）从气管小静脉渗漏。泄漏在3-4分钟达到峰值，并解决了10分钟。高分辨率共聚焦显微镜显示存在的焦点间隙在泄漏的小静脉细胞间连接。基因工程血管紧张素-1 *，通过腺病毒转导肝脏系统传递，减少了69%的500纳米微球后缓激肽泄漏。渗漏的减少与内皮间隙的数量和大小的减少一致。微静脉表面内皮间隙所占比例减少61%。微球泄漏与间隙数量和尺寸密切相关（r（2）= 0.89）。总之，结果表明，Ang-1通过影响细胞内信号传导、细胞骨架和连接相关分子来限制在内皮细胞连接处形成的间隙的数量和大小，从而减少从发炎的小静脉的渗漏。
Angiopoietin-1 (Ang-1) is essential for remodeling of the primitive vascular plexus and recruitment of mural cells during embryonic development. In the adult vasculature, Ang-1 can reduce plasma leakage in inflammation, but the mechanism of this action is not well understood. In the present study, we determined the magnitude and cellular mechanism of the antileak effect of Ang-1 in the airways of mice. Intravenous injection of bradykinin resulted in leakage of fluorescent microspheres (diameter 25 - 1,000 nm) from tracheal venules. The leakage peaked in 3-4 min and resolved by 10 min. High-resolution confocal microscopy revealed the presence of focal gaps at intercellular junctions of leaky venules. Genetically engineered Ang-1*, delivered systemically by adenoviral transduction of the liver, reduced leakage of 500-nm microspheres after bradykinin by 69%. The reduction in leakage coincided with a decrease in number and size of endothelial gaps. The proportion of venular surface occupied by endothelial gaps decreased 61%. Microsphere leakage correlated strongly with gap number and size (r(2) = 0.89). Together the results suggest that Ang-1 reduces leakage from inflamed venules by restricting the number and size of gaps that form at endothelial cell junctions through effects on intracellular signaling, cytoskeleton, and junction- related molecules.