Abstract 4359: Use of high resolution Doppler imaging for non-invasive, quantitative evaluation of hypoxia-driven neovascularization following surgical ligation of the femoral artery

Abstract

Abstract A tumor's growth is inextricably linked with its vascularization. Rapidly growing tumors outstrip their blood supply, creating hypoxia. To compensate, tumor cells release angioproliferative factors that stimulate endothelial cell proliferation. Proliferating endothelial cells contribute to the formation of new blood vessels that promote tumor perfusion and stimulate further tumor growth. The close link between tumor growth and neovascularization makes it difficult to study either process in the absence of the other. To address this we have adapted a mouse model used in the study of peripheral arterial disease. Ischemia was induced by surgical ligation and excision a 3-5mm portion of the femoral artery, vein, and all nearby arterial branches in the right hindlimb of 10-12 week old athymic nude mice. Limb perfusion was measured prior to surgery and 1, 7, 14, 21, and 28 days post-surgery. A 7mm portion of hindlimb perfusion was quantified using Power Doppler mode on the VisualSonics Vevo 770 High Resolution micro Ultrasound system. Morphological changes were observed by histology and immunohistochemistry using antibodies against CD31 and F4/80. Based on quantified Doppler ultrasound data, limb perfusion was reduced as much as 80% within 24 hrs of ligation. Blood flow was restored over the course of the next 7 days. However, re-perfused limbs showed a diffuse pattern of blood flow in comparison to control limbs. Loss of perfusion was accompanied by muscle atrophy and the accumulation of intra-fasicular fat deposits. IHC revealed a marked increase of F4/80 and CD31 staining in ligated limbs. Similar changes were not observed in contralateral limbs that were not operated on or in sham-ligated hind limbs. Our data is consistent with the interpretation that femoral artery ligation causes acute loss of perfusion that is compensated for by macrophage recruitment and disseminated neovascularization. This model provides a novel opportunity to study neovascularization in the absence of tumor growth that will complement ongoing studies using tumor-based models of angiogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4359. doi:1538-7445.AM2012-4359