title: 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.
abstract: 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 (99m)Tc-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.
authors: Department of Medicine, Columbia University Medical Center, New York, NY, USA.
authors: Yared
authors: Y
authors: Tekabe
authors: Department of Medicine, Columbia University Medical Center, New York, NY, USA.
authors: Tamykah
authors: T
authors: Anthony
authors: Department of Medicine, Columbia University Medical Center, New York, NY, USA.
authors: Qing
authors: Q
authors: Li
authors: Institute of Life Sciences, Department of Biotechnology, Bhubaneswar, India.
authors: Rashmi
authors: R
authors: Ray
authors: Institute of Life Sciences, Department of Biotechnology, Bhubaneswar, India.
authors: Vivek
authors: V
authors: Rai
authors: Department of Medicine, Columbia University Medical Center, New York, NY, USA.
authors: Geping
authors: G
authors: Zhang
authors: Department of Medicine, New York University Medical Center, New York, NY, USA.
authors: Ann Marie
authors: AM
authors: Schmidt
authors: Department of Medicine, Columbia University Medical Center, New York, NY, USA lj2129@columbia.edu.
authors: Lynne L
authors: LL
authors: Johnson
mesh_terms: D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003925:Diabetic Angiopathies / Q000188:drug therapy / Q000209:etiology; D005263:Femoral Artery; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000188:drug therapy*; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D000067759:Receptor for Advanced Glycation End Products / Q000276:immunology*
chemical_list: D000906:Antibodies; D000067759:Receptor for Advanced Glycation End Products
keywords: angiogenesis; anti-RAGE antibody; diabetes