Analysis of In Situ and Ex Vivo Vascular Endothelial Growth Factor Receptor Expression During Experimental Aortic Aneurysm Progression

Objective—Mural inflammation and neovascularization are characteristic pathologic features of abdominal aortic aneurysm (AAA) disease. Vascular endothelial growth factor receptor (VEGFR) expression may also mediate AAA growth and rupture. We examined VEGFR expression as a function of AAA disease progression in the Apolipoprotein E- deficient (Apo E−/−) murine AAA model. Methods—Apo E−/ − mice maintained on a high fat diet underwent continuous infusion with angiotensin II at 1000 ng/kg/min (Ang II) or vehicle (Control) via subcutaneous osmotic pump. Serial transabdominal ultrasound measurements of abdominal aortic diameter were recorded (n = 16 mice, 3 – 4 time points / mouse) for up to 28 days. Near-infrared receptor fluorescent (NIRF) imaging was performed on Ang II mice (n = 9) and Controls (n=5) with scVEGF/Cy, a single-chain VEGF homo-dimer labeled with Cy5.5 fluorescent tracer (7–18 µg/mouse IV). NIRF with inactivated single chain VEGF/Cy tracer (scVEGF/In, 18 µg/mouse IV) was performed on two additional Ang II mice to control for non-receptor mediated tracer binding and uptake. Following image acquisition and sacrifice, aortae were harvested for analysis. An additional AAA mouse cohort received either a