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

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Abstract
Objective— Mural inflammation and neovascularization are characteristic pathological 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 and Results— 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 to 4 time points per 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 to 18 μg/mouse IV). NIRF with inactivated single chain VEGF/Cy tracer (scVEGF/In, 18 μg/mouse IV) was perform... VEGFR expression was examined as a function of experimental AAA progression. VEGFR fluorescent signal intensity increased in a diameter-dependent fashion in aneurysmal aortae. VEGFR-2 expression localized to medial smooth muscle cells. Angiogenesis inhibition limited AAA progression. Clinical VEGFR expression imaging may prove useful in evaluating therapies for AAA disease.

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