Abstract 642: Vascular Endothelial Growth Factor Receptor 2 Blockade in Murine Vein Graft Ameliorates Lesion Growth and Enhances Plaque Stability by Reducing Intraplaque Hemorrhage
| Autor: | Margreet R de Vries, Rob C de Jong, Erna A Peters, Jaap F Hamming, Marie-José Goumans, Paul H Quax |
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| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 34 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/atvb.34.suppl_1.642 |
| Popis: | 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 form of leaky vessels in the DC101 treated group. This was accompanied by a significant 25-fold decrease in extravasated erythrocytes. Furthermore, lesions that exhibit intraplaque hemorrhage showed a strong increase in Ang-2, indicative for immature neovessels. VEGFR2 blockade however, did not affect the neovessel density in the lesions (control 52±19 neovessels/section; DC101 63±25 neovessels/section). Interestingly, the vein graft lesion area in the DC101 group was significantly reduced with 32% compared to the control group. Moreover, plaque stability was clearly increased in DC101 treated mice, determined by a 25% reduction in macrophage content, a 50% increase in collagen content and a 120% increase in SMC content. Blockade of VEGFR2 leads to reduced intraplaque hemorrhage, decreased vein graft lesion area and increased plaque stability. This identifies plaque neovascularization as an attractive target for the treatment of unstable atherosclerotic diseases. |
| Databáze: | OpenAIRE |
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