Angiopoietin-1 protects the adult vasculature against plasma leakage

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Abstract
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 factor1 (VEGF) and the angiopoietins2 function together during vascular development, with VEGF acting early during vessel formation3,4,5, and angiopoietin-1 acting later during vessel remodeling, maturation and stabilization6,7,8,9. Although VEGF was initially called vascular permeability factor10,11, 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,​ 13,​ 14), and have shown that transgenic angiopoietin-1 acts reciprocally as an anti-permeability factor when provided chronically during vessel formation14, although it also profoundly affects vascular morphology when thus delivered14,15. 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.