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 PS194. VEGF-A Neutralization Suppresses Experimental Abdominal Aortic Aneurysm (AAA) Formation

Keith J. Glover, Baohui Xu, Yasunori Iida, Haojun Xuan, Hiroki Tanaka, Wei Wang, Naoki Fujimura, Mary Gerritsen, Ronald L. Dalman
Stanford University School of Medicine, Stanford, CA.
OBJECTIVES: Aortic mural angiogenesis is a key pathologic feature of AAA disease. We previously reported that VEGF-receptor 2 expression correlated with experimental AAA progression. This study evaluated the influence of anti-VEGF-A monoclonal antibody (mAb) therapy on AAA formation and progression in the porcine pancreatic elastase (PPE) infusion model in C57Bl/6J mice.
METHODS: PPE-infused mice were given anti-VEGF-A neutralizing mAb or control mAb. Aortic aneurysm progression was evaluated via serial transabdominal in vivo ultrasonography and histology at sacrifice.
RESULTS: In control mAb-treated mice, persistent and significant aortic enlargement was noted beginning the third day following PPE infusion. Anti-VEGF-A mAb treatment initiated 3 days prior to PPE infusion significantly attenuated PPE-induced aortic expansion. Histologically, the VEGA-A neutralization resulted in preserved medial smooth muscles and elastin, and reduced mural leukocyte infiltration and angiogenesis. Although anti-VEGF-A mAb treatment initiated 5 days following PPE infusion reduced mural inflammation, aortic diameters continued to enlarge.
CONCLUSIONS: Anti-VEGF-A mAb prevents the initiation and subsequent progression of experimental AAAs. The mAb treatment has limited effects on existing aneurysms.
AUTHOR DISCLOSURES: M. Gerritsen: Nothing to disclose; R. L. Dalman: Nothing to disclose; N. Fujimura: Nothing to disclose; K. J. Glover: Nothing to disclose; Y. Iida: Nothing to disclose; H. Tanaka: Nothing to disclose; W. Wang: Nothing to disclose; B. Xu: Nothing to disclose; H. Xuan: Nothing to disclose.

Post April 2013

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