Journal Article

Treatment effect with anti-RAGE F(ab′)2 antibody improves hind limb angiogenesis and blood flow in Type 1 diabetic mice with left femoral artery ligation

Rai, Vivek, Zhang, Geping, Schmidt, Ann Marie, Tekabe, Yared, Anthony, Tamykah, Li, Qing, Ray, Rashmi, Johnson, Lynne L

2015

Overview

We investigated treatment with a receptor for advanced glycation endproduct (RAGE) blocking antibody on angiogenic response to hind limb ischemia in diabetic mice. Streptozotocin treated C57BL/6 mice received either murine monoclonal anti-RAGE F(ab′)2 intraperitoneally (n=10) or saline (n=9) for 9 weeks. Diabetic plus 10 non-diabetic C57BL/6 mice underwent left femoral artery ligation and 5 days later angiogenesis imaging with 99mTc-Arg–Gly–Asp (RGD) nanoSPECT/CT. Twenty-four days later, hind limb blood flow was measured with ultrasound, the mice were euthanized, and tissue was taken for immunohistochemistry. The angiogenic imaging signal in ischemic limbs was higher in RAGE-ab treated versus saline treated mice at day 5 (3.1±1.4 vs 1.68±0.35, p=0.02) and blood flow was higher at day 24 (1.49±0.5 vs 0.61±0.39, p=0.04). Immunohistochemistry of ischemic muscles showed greater capillary density in the RAGE-ab treated group versus the vehicle-treated group (p<0.001) (NS from non-diabetic mice). In conclusion, treatment with anti-RAGE F(ab′)2 in diabetic mice improves neovascularization in the ischemic leg.

• Publisher: SAGE Publications,Sage Publications Ltd
• Subject: Animals / Antibodies - therapeutic use / Diabetes Mellitus, Experimental / Diabetes Mellitus, Type 1 - complications / Diabetic Angiopathies - drug therapy / Diabetic Angiopathies - etiology / Femoral Artery / Hindlimb - blood supply / Ischemia - drug therapy / Ligation / Male / Mice / Mice, Inbred C57BL / Neovascularization, Physiologic - drug effects / Receptor for Advanced Glycation End Products - immunology