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Am J Physiol Heart Circ Physiol 284: H2124-H2135, 2003. First published January 30, 2003; doi:10.1152/ajpheart.00894.2002
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Vol. 284, Issue 6, H2124-H2135, June 2003

Structural mechanisms of acute VEGF effect on microvessel permeability

Bingmei M. Fu1,2 and Shang Shen1

1 Department of Mechanical Engineering and 2 Cancer Institute, University of Nevada, Las Vegas, Las Vegas, Nevada 89154

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 (Lp) 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 (alpha -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, alpha -lactalbumin, and BSA, respectively, within 30 s, and all returned to control within 2 min. On the basis of Lp (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.

solute permeability; frog; model for interendothelial cleft


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