Vascular endothelial growth factor affects the permeability of
brain microvessel endothelial cells in vitro.
Wang, Wen, Marsha J. Merrill, and Ronald T. Borchardt.
Department of Pharmaceutical Chemistry, The University of Kansas,
Lawrence, Kansas 66047, Surgical Neurology Branch, National Institute
of Neurological Disorders and Stroke, NIH, Bethesda, Maryland
20892
APStracts 3:0239C, 1996.
Vascular endothelial growth factor (VEGF), which stimulates
endothelial cell growth and induces hyperpermeability of the
microvasculature, plays an important role in normal- and tumor
-vasculature development and tumor edema generation. In this study, we
investigated the effect of VEGF on the permeability of cultured
bovine brain microvessel endothelial cells (BMECs), an in vitro
blood-brain barrier (BBB) model. We found that addition of purified
VEGF to both the apical and basolateral sides of the BMEC monolayers
increased the permeability of the monolayer to 14C-sucrose (about 3
-fold). A more significant increase in permeability was observed when
VEGF was applied to the basolateral side of the monolayer (3-fold)
than to the apical side (1.5-fold). The permeability-increasing
activity of VEGF on the BMEC monolayers is both dose- and time-
dependent. The VEGF-induced permeability increase in BMECs requires a
long incubation time with VEGF, and the effect is durable. These
results suggest that this cell culture system may be useful for
exploring the role of VEGF in regulating the permeability of the BBB,
for studying the mechanism of the permeability-increasing effect of
VEGF on the endothelial cells, and for evaluating the strategies to
regulate its activity.
Received 28 December 1995; accepted in final form 8 July 1996.
APS Manuscript Number C766-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 August 1996