Structural mechanisms of acute VEGF effect on microvessel permeability

Abstract

To investigate the ultrastructural mechanisms of acute microvessel hyperpermeability by vascular endothelial growth factor (VEGF), we combined a mathematical model ( J Biomech Eng 116: 502–513, 1994) with experimental data of the effect of VEGF on microvessel hydraulic conductivity ( L p) and permeability of various-sized solutes. We examined the effect of VEGF on microvessel permeability to a small solute (sodium fluorescein, Stokes radius 0.45 nm), an intermediate solute (α-lactalbumin, Stokes radius 2.01 nm), and a large solute [albumin (BSA), Stokes radius 3.5 nm]. Exposure to 1 nM VEGF transiently increased apparent permeability to 2.3, 3.3, and 6.2 times their baseline values for sodium fluorescein, α-lactalbumin, and BSA, respectively, within 30 s, and all returned to control within 2 min. On the basis of L p (DO Bates and FE Curry. Am J Physiol Heart Circ Physiol 271: H2520–H2528, 1996) and permeability data, the prediction from the model suggested that the most likely structural changes in the interendothelial cleft induced by VEGF would be a ∼2.5-fold increase in its opening width and partial degradation of the surface glycocalyx.