Abstract 1339: Tumor Necrosis Factor Receptor-2 Plays a Critical Role for Induction of Post Ischemic Neovascularization in Mouse Model of Hind Limb Ischemia
Background: Tumor necrosis factor alpha (TNF-α) is expressed in ischemic and necrotic tissue and is known to modulate angiogenesis. However the effect of TNF receptors on angiogenesis is not known. Using a mouse model of hind limb ischemia we studied the essential role of TNF receptor subtype 2 (TNFR2) in induction of angiogenesis.
Methods: Hind limb ischemia was induced by ligation of femoral artery in 8 weeks old wild and TNFR2−/− mice. The recovery in tissue perfusion was evaluated using the thermography analysis once a week. At the end of 4 weeks they were subjected to indocyanine green (ICG) fluorescence angiography to observe the angiogenesis. Samples were obtained to estimate the expression of angiogenic factors from both the groups.
Results: Follow-up observation revealed an improvement in the perfusion area of the ischemic limb, probably due to neovascularization and collateral growth induced by ischemia in wild mice (n=13). In contrast such an improvement was not observed in the TNFR2−/− mice (n=10) (Figure⇓). ICG fluorescence angiography at the end of 4 weeks confirmed angiogenesis in the ischemic limb in wild mice which was not seen in the TNFR2−/− mice (Figure⇓). Moreover, the expression of angiogenic factors such as VEGF and HIF-1α were significantly suppressed in the TNFR2−/− mice compared to that in the wild mice.
Conclusion: The present study demonstrates the critical role for TNFR2 in post ischemic recovery and hence modulation of TNFR2 could be of a valid clinical importance.