Magnetic resonance angiography reveals therapeutic enlargement of collateral induced by VEGF in a murine model of peripheral arterial disease

Purpose: To quantify spontaneous and therapeutic arteriogenesis in vivo in a murine model of peripheral arterial disease using magnetic resonance angiography. Materials and Methods: Male, 8-12-week-old, C57/BL6 mice underwent femoral-artery ligation; 21 days later, 2 mg/kg recombinant murine VEGF(165), 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 mm(2), P < 0.01). VEGF also induced angiogenesi (PECAM 1 levels 19 1% of vehicle, P < 0.05), and increased blood flow specific to the injection site (57 vs. 7 mL/minute/ 100 g, P < 0.05). Conclusion: 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.