Impaired autonomic regulation of resistance arteries in mice with low vascular endothelial growth factor or upon vascular endothelial growth factor trap delivery.
BACKGROUND
Control of peripheral resistance arteries by autonomic nerves is essential for the regulation of blood flow. The signals responsible for the maintenance of vascular neuroeffector mechanisms in the adult, however, remain largely unknown.


RESULTS
Here, we report that VEGF( partial differential/ partial differential) mice with low vascular endothelial growth factor (VEGF) levels suffer defects in the regulation of resistance arteries. These defects are due to dysfunction and structural remodeling of the neuroeffector junction, the equivalent of a synapse between autonomic nerve endings and vascular smooth muscle cells, and to an impaired contractile smooth muscle cell phenotype. Notably, short-term delivery of a VEGF inhibitor to healthy mice also resulted in functional and structural defects of neuroeffector junctions.


CONCLUSIONS
These findings uncover a novel role for VEGF in the maintenance of arterial neuroeffector function and may help us better understand how VEGF inhibitors cause vascular regulation defects in cancer patients.
Storkebaum
Erik
E
Vesalius Research Center, KU Leuven and VIB, Leuven, Belgium.
Ruiz de Almodovar
Carmen
C
Meens
Merlijn
M
Zacchigna
Serena
S
Mazzone
Massimiliano
M
Vanhoutte
Greet
G
Vinckier
Stefan
S
Miskiewicz
Katarzyna
K
Poesen
Koen
K
Lambrechts
Diether
D
Janssen
Ger M J
GM
Fazzi
Gregorio E
GE
Verstreken
Patrik
P
Haigh
Jody
J
Schiffers
Paul M
PM
Rohrer
Hermann
H
Van der Linden
Annemie
A
De Mey
Jo G R
JG
Carmeliet
Peter
P
D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000235:genetics / Q000503:physiopathology*; D002318:Cardiovascular Diseases / Q000235:genetics / Q000503:physiopathology*; D017536:Carotid Artery, Common / Q000294:innervation / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D018014:Gene Transfer Techniques; D007763:Lac Operon; D008638:Mesenteric Arteries / Q000294:innervation / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism; D014655:Vascular Resistance / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology*
D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2