Involvement of nitric oxide in angiogenic activities of vascular endothelial growth factor isoforms.
We compared effects of vascular endothelial growth factor-121 (VEGF121) and vascular endothelial growth factor-165 (VEGF165) on generation of NO in HUVEC and the involvement of NO in VEGF121- and VEGF165-induced angiogenesis. VEGF stimulated synthesis of NO within seconds, reaching peak concentrations of 450 +/- 25 and 180 +/- 15 nmol/l for VEGF121, and VEGF165, respectively. The VEGF121 increased NO production for about 40 s while VEGF165-stimulated NO release lasted only for about 20 s. Accordingly, cGMP elevation was stronger in VEGF121- than in VEGF165-treated cells. The VEGF121 was a very weak mitogen but strong chemoattractant for HUVEC, whereas VEGF165 potently induced both cell proliferation and migration. NO appeared to be involved in the endothelial migration and morphogenesis but not in the proliferation. NO was also a permissive molecule for VEGF121- but not for VEGF165-induced capillary sprouting in spheroid culture. In conclusion, VEGF121 is a stronger stimulator of endothelial nitric oxide synthase (eNOS) activity, and angiogenic potential of VEGF121 is more reliant on NO contribution.
Józkowicz
Alicja
A
Department of Vascular Surgery, General Hospital, University of Vienna, Vienna, Austria.
Dulak
Józef
J
Nigisch
Anneliese
A
Funovics
Philipp
P
Weigel
Guenter
G
Polterauer
Peter
P
Huk
Ihor
I
Malinski
Tadeusz
T
D017398:Alternative Splicing; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000032:analysis; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D014644:Genetic Variation; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000235:genetics; D009569:Nitric Oxide / Q000096:biosynthesis*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology; D042442:Vascular Endothelial Growth Factors
D020033:Protein Isoforms; D011994:Recombinant Proteins; D042442:Vascular Endothelial Growth Factors; D009569:Nitric Oxide; D006152:Cyclic GMP