EXPRESSION OF VEGF RECEPTORS IN ARTERIES AFTER ENDOTHELIAL INJURY ANDLACK OF INCREASED ENDOTHELIAL REGROWTH IN RESPONSE TO VEGF

Vascular endothelial growth factor (VEGF) is an endothelial cell-speci fic factor with angiogenic effects in vivo and mitogenic effects in vi tro. Administration of VEGF has been reported to stimulate endothelial growth in denuded arteries and new blood vessel formation in models o f induced tissue ischemia. In the present study, expression of VEGF an d its receptors flk-1 and flt-1 was determined in injured aortas and c arotid arteries of rats and mice. Neither VEGF nor flk-1 mRNA was dete ctable in vascular cells. mRNA levels for flt-1 were dramatically upre gulated 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-1 expression, VEGF increased permeability. These areas revealed a loss of endothelial contacts at the ultrastructural level. These fi ndings suggest that VEGF is not a direct mitogen for large-vessel endo thelium in vivo and that VEGF may play a role in abolishing contact in hibition, which may be a prerequisite for endothelial proliferation.