Yasunori Iida2, Baohui Xu1, Xiaolei Hu1, Vinca Chow1, Richard Yuan1, Mary Gerritsen1, Hitoshi Ogino2, Ronald L. Dalman1
1Stanford University School of Medicine, Stanford, CA; 2Tokyo Medical University, Tokyo, Japan.
OBJECTIVES: Mural angiogenesis is a prominent pathologic feature in abdominal aortic aneurysm (AAA) disease. We evaluated the effect of sunitinib, an FDA-approved angiogenesis inhibitor, on the formation and progression of experimental AAA.
METHODS: AAAs were created via by intraaortic PPE infusion in 10-wk-old male C57BL/6 mice. Oral sunitinib (or vehicle alone) was administered either from 1) 3 days prior to PPE infusion, or 2) 5 days thereafter ̶ until sacrifice. Aortic diameter was serially monitored via ultrasound, and aortae harvested for histopathology at 14 days.
RESULTS: AAA (defined as ≥50% diameter increase) developed in all vehicle-treated mice (n=4-7 mice). Sunitinib treatment initiated prior to PPE infusion at 4, 20 or 100 mg/kg/day prevented AAA formation (n=3-7 mice). Additionally, sunitinib initiated after PPE infusion at 4 or 100 mg/kg stabilized and reduced AAA diameter, respectively, compared to immediate pre-treatment diameter. Sunitinib preserved aortic medial elastin and smooth muscle cellularity, while reducing medial/adventitial angiogenesis and monocytes/macrophages density.
CONCLUSIONS: Sunitinib therapy suppresses AAA formation, as well as stabilizing or regressing aortic diameter in existing aneurysms in a dose-dependent fashion. Similar strategies may prove effective in suppressing or stabilizing early AAA disease.
AUTHOR DISCLOSURES: V. Chow, Nothing to disclose; R. L. Dalman, Nothing to disclose; M. Gerritsen, Nothing to disclose; X. Hu, Nothing to disclose; Y. Iida, Nothing to disclose; H. Ogino, Nothing to disclose; B. Xu, Nothing to disclose; R. Yuan, Nothing to disclose.
Posted April 2012