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 microvascular permeability to plasma proteins. However, the vessel types (arteriolar, venular, and capillary) affected by VEGF and the modification of endothelial morphology in response to increased permeability induced by VEGF in vivo have not been precisely documented. By topical application or intradermal injection of recombinant human VEGF-165 we find that VEGF increases the permeability of postcapillary venules as well 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 beds which do not normally have fenestrated endothelium, namely the cremaster muscle and skin. Histamine, saline, and heat-inactivated VEGF do not cause fenestrations. Increased permeability is completely inhibited when VEGF is cleared by immunoprecipitation with anti-VEGF monoclonal antibodies. The VEGF effect on permeability is unlike that of any other mediator described to date since both muscular venules and capillaries are affected.
Roberts
W G
WG
University of California-San Diego, La Jolla 92093-0651, USA.
Palade
G E
GE
D000818:Animals; D002450:Cell Communication / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects*; D016228:Endothelial Growth Factors / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D008222:Lymphokines / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008833:Microcirculation / Q000187:drug effects* / Q000502:physiology; D008854:Microscopy, Electron; D018482:Muscle, Skeletal / Q000098:blood supply*; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000494:pharmacology; D012867:Skin / Q000098:blood supply*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors