Journal
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
Volume 1760, Issue 9, Pages 1465-1474Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbagen.2006.06.010
Keywords
vascular endothelial growth factor; extracellular matrix; perlecan; proteoglycan; heparan sulfate; endothelial cell
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A member of the vascular endothelial growth factor (VEGF) family, VEGF 165, regulates vascular endothelial cell functions in autocrine and paracrine fashions in microvessels. Proteoglycans are highly glycosylated poly-anionic macromolecules that influence cellular behaviors such as proliferation and migration by interacting with cytokines/growth factors. In the present study, we investigated the regulation of proteoglycan synthesis by VEGF 165 in cultured human brain microvascular endothelial cells. The cells were exposed to recombinant human VEGF 165, and the proteoglycans were then characterized using biochemical techniques. VEGF165 treatment increased the accumulation of proteoglycans 1.4- and 1.6-fold in the cell layer and conditioned medium, respectively. This effect resulted from the activation of VEGFR-2, and was mimicked by vammin, a VEGFR-2 ligand from snake venom but not placenta growth factor, which binds specifically to VEGFR-1. VEGF165 stimulated the production and secretion of perlecan, substituted with shorter heparan sulfate side chains, but with unaltered sulfated disaccharide composition. The perlecan secreted by VEGF 165-stimulated endothelial cells may be involved in the regulation of cellular behavior during angiogenesis, in diseases of the brain microvessels, and in the maintenance of the endothelial cell monolayer. (c) 2006 Elsevier B.V. All rights reserved.
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