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