Magnetic resonance angiography reveals therapeutic enlargement of collateral vessels induced by VEGF in a murine model of peripheral arterial disease.
OBJECTIVE
To quantify spontaneous and therapeutic arteriogenesis in vivo in a murine model of peripheral arterial disease using magnetic resonance angiography.


METHODS
Male, 8-12-week-old, C57/BL6 mice underwent femoral artery ligation; 21 days later, 2 mg/kg recombinant murine VEGF165, formulated for slow release, was injected into the ipsilateral gastrocnemius. The spontaneous (following ligation) and therapeutic (following vascular endothelial growth factor (VEGF)) formation of collateral vessels was quantified using 3D magnetic resonance angiography on a small-bore 4.7T system. Therapeutically induced angiogenesis and blood flow were quantified using an in situ anti-platelet endothelial cell adhesion molecule (PECAM) 1 radioimmunoassay and radiolabeled microsphere deposition, respectively.


RESULTS
Spontaneous arteriogenesis was visible in all animals five days after ligation. VEGF treatment doubled the arteriogenic response five days after treatment compared to vehicle (cross-sectional area of vessels: 0.96 vs. 0.46 mm2, P<0.01). VEGF also induced angiogenesis (PECAM1 levels 191% of vehicle, P<0.05) and increased blood flow specific to the injection site (57 vs. 7 mL/minute/100 g, P<0.05).


CONCLUSIONS
The presented methodology allowed in vivo quantification of spontaneous arteriogenesis in a murine model of peripheral arterial disease and demonstrated that therapeutic enlargement of collateral vessels is possible with VEGF.
Greve
Joan M
JM
Department of Biomedical Imaging, Genentech, Inc., South San Francisco, California 94080, USA. jgreve@gene.com
Chico
Timothy J
TJ
Goldman
Hope
H
Bunting
Stuart
S
Peale
Franklin V
FV
Daugherty
Ann
A
van Bruggen
Nicholas
N
Williams
Simon P
SP
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects*; D003097:Collateral Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D016491:Peripheral Vascular Diseases / Q000188:drug therapy* / Q000473:pathology*; D011379:Prognosis; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage*
D042461:Vascular Endothelial Growth Factor A