INCREASED MICROVASCULAR PERMEABILITY AND ENDOTHELIAL FENESTRATION INDUCED BY VASCULAR ENDOTHELIAL GROWTH-FACTOR

The vascular endothelial growth factor (VEGF) was originally described as vascular permeability factor due to its ability to increase microv ascular permeability to plasma proteins. However, the vessel types (ar teriolar, venular, and capillary) affected by VEGF and the modificatio n of endothelial morphology in response to increased permeability indu ced by VEGF in vivo have not been precisely documented. By topical app lication or intradermal injection of recombinant human VEGP-165 we fin d that VEGF increases the permeability of postcapillary venules as wel l as muscular venules and capillaries. Surprisingly, we also find that endothelia of small venules and capillaries become fenestrated within 10 minutes of VEGF application. Fenestrations appeared in vascular be ds which do not normally have fenestrated endothelium, namely the crem aster muscle and skin. Histamine, saline, and heat-inactivated VEGF do not cause fenestrations. Increased permeability is completely inhibit ed when VEGF is cleared by immunoprecipitation with anti-VEGF monoclon al antibodies. The VEGF effect on permeability is unlike that of any o ther mediator described to date since both muscular venules and capill aries are affected.