Abstract 642: Vascular Endothelial Growth Factor Receptor 2 Blockade in Murine Vein Graft Ameliorates Lesion Growth and Enhances Plaque Stability by Reducing Intraplaque Hemorrhage

Immature plaque neovessels contribute to atherosclerotic plaque instability and intraplaque hemorrhage by leaking erythrocytes and leukocytes in the plaque. Vascular Endothelial Growth Factor Receptor 2 (VEGFR2), together with the angiopoietin (Ang)-Tie2 system, regulates the maturation of neovessels. We have previously shown that murine vein graft lesions exhibit massive plaque neovascularization and that intraplaque hemorrhage contributes to lesion growth. We hypothesized that blockade of VEGFR2 results in more mature plaque microvessels and less intraplaque hemorrhage. Donor caval veins were engrafted in carotid arteries of recipient hypercholesterolemic ApoE3*Leiden mice (n=14/group). Mice were treated at day 14, 17, 21 and 25 with VEGFR2 blocking antibodies (DC101) or control IgG antibodies (10 mg/kg). At day 28 mice were sacrificed for histological analysis of the vein grafts. Morphometric analysis revealed a striking 50% decrease in vein graft segments that expressed intraplaque hemorrhage in the f...