Reevaluation of the role of VEGF-B suggests a restricted role in the revascularization of the ischemic myocardium.
OBJECTIVE
The endogenous role of the VEGF family member vascular endothelial growth factor-B (VEGF-B) in pathological angiogenesis remains unclear.


RESULTS
We studied the role of VEGF-B in various models of pathological angiogenesis using mice lacking VEGF-B (VEGF-B(-/-)) or overexpressing VEGF-B(167). After occlusion of the left coronary artery, VEGF-B deficiency impaired vessel growth in the ischemic myocardium whereas, in wild-type mice, VEGF-B(167) overexpression enhanced revascularization of the infarct and ischemic border zone. By contrast, VEGF-B deficiency did not affect vessel growth in the wounded skin, hypoxic lung, ischemic retina, or ischemic limb. Moreover, VEGF-B(167) overexpression failed to enhance vascular growth in the skin or ischemic limb.


CONCLUSIONS
VEGF-B appears to have a relatively restricted angiogenic activity in the ischemic heart. These insights might offer novel therapeutic opportunities.
Li
Xuri
X
Vesalius Research Center, VIB, 3000 Leuven, Belgium.
Tjwa
Marc
M
Van Hove
Inge
I
Enholm
Berndt
B
Neven
Elke
E
Paavonen
Karri
K
Jeltsch
Michael
M
Juan
Toni Diez
TD
Sievers
Richard E
RE
Chorianopoulos
Emmanuel
E
Wada
Hiromichi
H
Vanwildemeersch
Maarten
M
Noel
Agnes
A
Foidart
Jean-Michel
JM
Springer
Matthew L
ML
von Degenfeld
Georges
G
Dewerchin
Mieke
M
Blau
Helen M
HM
Alitalo
Kari
K
Eriksson
Ulf
U
Carmeliet
Peter
P
Moons
Lieve
L
D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006614:Hindlimb; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D008168:Lung / Q000098:blood supply; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D018482:Muscle, Skeletal / Q000098:blood supply; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011994:Recombinant Proteins / Q000378:metabolism; D012171:Retinal Vessels / Q000378:metabolism; D012867:Skin / Q000098:blood supply; D015854:Up-Regulation; D042561:Vascular Endothelial Growth Factor B / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
D043925:Angiogenesis Inducing Agents; D011994:Recombinant Proteins; C467485:VEGFB protein, human; D042561:Vascular Endothelial Growth Factor B; C467482:vascular endothelial growth factor B, mouse; C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1