Vascularendothelialgrowthfactor(VEGForVEGFA),alsoknownasvascularpermeABIlityfactor(VPF),isapotentmediatorofbothangiogenesisandvasculogenesisinthefetusandadult(13).ItisamemberofthePDGFfamilythatischaracterizedbythepresenceofeightconservedcysteineresiduesandacysteineknotstructure(4).Humansexpressalternatelysplicedisoformsof121,145,165,183,189,and206aminoacids(aa)inlength(4).VEGF165appearstobethemostabundantandpotentisoform,followedbyVEGF121andVEGF189(3,4).

VEGF121istheonlyformthatlacksabasicheparinbindingregionandisfreelydiffusIBLe(4).Mouseembryosexpressingonlythecorrespondingisoform(VEGF120)donotsurvivetoterm,andshowdefectsinskeletogenesis(5).HumanVEGF121shares87%aasequenceidentitywithcorrespondingregionsofmouseandrat,93%withfeline,equineandbovine,and91%,95%and96%withovine,canineandporcineVEGF,respectively.VEGFbindsthetypeItransmembranereceptortyrosinekinasesVEGFR1(alsocalledFlt1)andVEGFR2(Flk1/KDR)onendothelialcells(4).AlthoughVEGFaffinityishighestforbindingtoVEGFR1,VEGFR2appearstobetheprimarymediatorofVEGFangiogenicactivity(3,4).VEGF165bindsthesemaphorinreceptor,Neuropilin1;VEGF121bindinghasalsobeenreported(6).VEGFisrequiredduringembryogenesistoregulatetheproliferation,migration,andsurvivalofendothelialcells(3,4).Inadults,VEGFfunctionsmainlyinwoundhealingandthefemalereproductivecycle(3).Pathologically,itisinvolvedintumorangiogenesisandvascularleakage(7,8).CirculatingVEGFlevelscorrelatewithdiseaseactivityinautoimmunediseasessuchasrheumatoidarthritis,multiplesclerosisandsystemiclupuserythematosus(9).VEGFisinducedbyhypoxiaandcytokinessuchasIL1,IL6,IL8,oncostatinMandTNFα(3,4,10). 

Refererences:

1.Leung,D.W.etal.(1989)Science246:1306.
2.Keck,P.J.etal.(1989)Science246:1309.
3.Byrne
8.Thurston,G.(2002)J.Anat.200:575.
9.Carvalho,J.F.etal.(2007)J.Clin.Immunol.27:246.
10.Angelo,L.S.andR.Kurzrock(2007)Clin.CancerRes.13:2825.