Angiopoietin-1 protects the adult vasculature against plasma leakage
Angiopoietin-1 protects the adult vasculature against plasma leakage
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DOI：
10.1038/74725
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发表时间：
2000-04-01
期刊：
影响因子：
82.9
通讯作者：
Yancopoulos, GD
中科院分区：
文献类型：
--
作者：
Thurston, G;Rudge, JS;Yancopoulos, GD
血管渗漏的病理性增加会导致水肿和肿胀，从而导致脑肿瘤、糖尿病性视网膜病变、中风后、败血症期间以及类风湿性关节炎和哮喘等炎症性疾病的严重问题。尽管许多药物和疾病过程会增加血管渗漏，但没有已知的药物能够特异性地使血管抵抗渗漏。血管内皮生长因子 (1) (VEGF) 和血管生成素 (2) 在血管发育过程中共同发挥作用，其中 VEGF 在血管形成早期发挥作用 (3-5)，而血管生成素-1 在血管重塑、成熟和稳定过程中后期发挥作用 (6-9)。尽管 VEGF 最初被称为血管通透性因子 (10,11)，但人们对其通透性作用的关注较少，而更多的精力致力于其参与血管生长以及在缺血和癌症中的应用。最近的转基因方法已证实 VEGF 具有深远的通透性影响（参考文献 12-14），并表明转基因血管生成素-1 在血管形成过程中长期提供时可起到抗渗透因子的作用 (14)，尽管如此输送时它也会深刻影响血管形态 (14,15)。为了在临床上有用，血管生成素-1 必须在急性给予成人血管时抑制渗漏，并且这种作用必须与其深刻的血管生成能力脱钩。在此，我们表明，急性施用 angiopoietin-1 确实可以保护成人脉管系统免于渗漏，从而对抗 VEGF 和炎症因子的潜在致命作用。
Pathological increases in vascular leakage lead to edema and swelling, causing serious problems in brain tumors, in diabetic retinopathy, after strokes, during sepsis and also in inflammatory conditions such as rheumatoid arthritis and asthma. Although many agents and disease processes increase vascular leakage, no known agent specifically makes vessels resistant to leaking. Vascular endothelial growth factor(1) (VEGF) and the angiopoietins(2) function together during vascular development, with VEGF acting early during vessel formation(3-5), and angiopoietin-1 acting later during vessel remodeling, maturation and stabilization(6-9). Although VEGF was initially called vascular permeability factor(10,11), there has been less focus on its permeability actions and more effort devoted to its involvement in vessel growth and applications in ischemia and cancer. Recent transgenic approaches have confirmed the profound permeability effects of VEGF (refs. 12-14), and have shown that transgenic angiopoietin-1 acts reciprocally as an anti-permeability factor when provided chronically during vessel formation(14) although it also profoundly affects vascular morphology when thus delivered(14,15). To be useful clinically angiopoietin-1 would have to inhibit leakage when acutely administered to adult vessels, and this action would have to be uncoupled from its profound angiogenic capabilities. Here we show that acute administration of angiopoietin-1 does indeed protect adult vasculature from leaking, countering the potentially lethal actions of VEGF and inflammatory agents.