Expression of VEGF receptors in arteries after endothelial injury and lack of increased endothelial regrowth in response to VEGF.
Vascular endothelial growth factor (VEGF) is an endothelial cell-specific factor with angiogenic effects in vivo and mitogenic effects in vitro. Administration of VEGF has been reported to stimulate endothelial growth in denuded arteries and new blood vessel formation in models of induced tissue ischemia. In the present study, expression of VEGF and its receptors flk-l and flt-l was determined in injured aortas and carotid arteries of rats and mice. Neither VEGF nor flk-l mRNA was detectable in vascular cells. mRNA levels for flt-l were dramatically upregulated at the leading edge of a growing endothelial monolayer in vivo; however, these cells did not demonstrate increased replication after VEGF infusion. Furthermore, all doses and treatment protocols of VEGF failed to promote reendothelialization in denuded arteries. At sites of flt-l expression, VEGF increased permeability. These areas revealed a loss of endothelial contacts at the ultrastructural level. These findings suggest that VEGF is not a direct mitogen for large-vessel endothelium in vivo and that VEGF may play a role in abolishing contact inhibition, which may be a prerequisite for endothelial proliferation.
Department of Surgery, Maine Medical Center Research Institute, South Portland 04106, USA. lindnv.mmcri@office.mmc.org
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D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D002404:Catheterization; D002455:Cell Division / Q000187:drug effects; D016228:Endothelial Growth Factors / Q000378:metabolism* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D017403:In Situ Hybridization; D008222:Lymphokines / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040281:Vascular Endothelial Growth Factor Receptor-1