Oneofthekeymoleculesforangiogenesisandforthesurvivaloftheendotheliumisvascularendothelialgrowthfactor(VEGF-A).ItisaspecificendothelialcellmitogenandastrongvascularpermeABIlityfactor(VPF).VEGF-Aisaheparin-bindingglycoprotein,secretedasahomodimerof45kDabymanydifferentcelltypes.VEGF-Aalsocausesvasodilationthroughthenitiricoxidesynthasepathwayinendothelialcellsandcanactivatemigrationinmonocytes.ManydifferentsplicevariantsofVEGF-Ahavebeendescribed,butVEGF165isthemostpredominantproteinandanchorswithitsheparinbindingdomaintoextracellularmatrixandtoheparinsulfate.ExampleswhereVEGF-Aplaysanimportantrolearepsoriasisandrheumatoidarthritis,aswellastheovarianhyperstimulationsyndrome.DiabeticretinopathyisassociatedwithhighintraocularlevelsofVEGF-A,andinhibitionofVEGF-Afunctionmayresultininfertilitybyblockageofcorpusluteumfunction.DirectdemonstrationoftheimportanceofVEGF-AintumorgrowthhasbeenachievedusingdominantnegativeVEGFreceptorstoblockinvivoproliferation,aswellasblockingantibodiestoVEGFortooneoftheVEGFreceptors.VEGF-AtranscriptionishighlyactivatedbyhypoxiaandbyoncogeneslikeH-rasandseveraltransmembranetyrosinekinases,suchasepidermalgrowthfactorreceptorandErbB2.TogetherthesepathwaysaccountforamarkedupregulationofVEGF-Aintumorscomparedtonormaltissuesandareoftenofprognosticimportanceandrelevance.
TargetingtheVEGFsignallingmaybeofmajortherapeuticimportanceformanydiseasesandservesasabasisforthedesignoffuture(anti)-angiogenictreatments.

Synonyms:VascularendothelialgrowthfactorA,VPF