VEGF-related protein isolated from Vipera palestinae venom, promotes angiogenesis.
Therapeutic angiogenesis is one of the major approaches in designing new therapies for cardiovascular diseases. vpVEGF was purified from Vipera palestinae venom using two steps of reverse-phase HPLC. Structurally, vpVEGF belongs to the VEGF-F1 family of snake venom proteins, and potently stimulated dHMVEC proliferation in a VEGFR-2 dependent manner. This growth factor appeared to be a chemoattractant for migration of these cells and stimulated their radial migration in a collagen gel. The stimulatory effect on dHMVEC was correlated with activation of the MAPK Erk1/2 signaling pathway. In vivo vpVEGF induced angiogenesis in a Japanese quail assay and in a Matrigel plug assay in mice. Although in the quail assay vpVEGF showed lower activity than hrVEGF-A165 in mammalian-related systems there were no significant differences. The experiments with dHMVEC, as well as angiogenesis in vivo suggest that the pro-angiogenic effect of vpVEGF is related to its interaction with VEGFR-2 (flk-1).
Brown
Meghan C
MC
Department of Neuroscience, Center for Neurovirology, School of Medicine, Temple University, 1900 N. 12th Street, Philadelphia, PA 19122, USA.
Calvete
Juan J
JJ
Staniszewska
Izabela
I
Walsh
Erin M
EM
Perez-Liz
Georgina
G
Del Valle
Luis
L
Lazarovici
Philip
P
Marcinkiewicz
Cezary
C
D000595:Amino Acid Sequence; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002633:Chemotaxis; D003094:Collagen / Q000737:chemistry; D003370:Coturnix; D004338:Drug Combinations; D042783:Endothelial Cells; D005260:Female; D007797:Laminin / Q000737:chemistry; D020935:MAP Kinase Signaling System; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic; D011509:Proteoglycans / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D014688:Venoms / Q000378:metabolism; D017819:Viperidae
D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D042461:Vascular Endothelial Growth Factor A; D014688:Venoms; C059485:matrigel; D003094:Collagen; D040301:Vascular Endothelial Growth Factor Receptor-2