Angiopoietin-1 protects the adult vasculature against plasma leakage

Pathological increases in vascular leakage lead to edema and swelling, caus ing serious problems in brain tumors, in diabetic retinopathy, after stroke s, during sepsis and also in inflammatory conditions such as rheumatoid art hritis and asthma. Although many agents and disease processes increase vasc ular leakage, no known agent specifically makes vessels resistant to leakin g. Vascular endothelial growth factor(1) (VEGF) and the angiopoietins(2) fu nction together during vascular development, with VEGF acting early during vessel formation(3-5), and angiopoietin-1 acting later during vessel remode ling, maturation and stabilization(6-9). Although VEGF was initially called vascular permeability factor(10,11), there has been less focus on its perm eability actions and more effort devoted to its involvement in vessel growt h and applications in ischemia and cancer. Recent transgenic approaches hav e confirmed the profound permeability effects of VEGF (refs. 12-14), and ha ve shown that transgenic angiopoietin-1 acts reciprocally as an anti-permea bility factor when provided chronically during vessel formation(14) althoug h 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 un coupled 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 inflammator y agents.