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Vascular endothelial growth factor enhances atherosclerotic plaque progression

Abstract

Vascular endothelial growth factor (VEGF) can promote angiogenesis but may also exert certain effects to alter the rate of atherosclerotic plaque development. To evaluate this potential impact on plaque progression, we treated cholesterol-fed mice doubly deficient in apolipoprotein E/apolipoprotein B100 with low doses of VEGF (2 μg/kg) or albumin. VEGF significantly increased macrophage levels in bone marrow and peripheral blood and increased plaque area 5-, 14- and 4-fold compared with controls at weeks 1, 2 and 3, respectively. Plaque macrophage and endothelial cell content also increased disproportionately over controls. In order to confirm that the VEGF-mediated plaque progression was not species-specific, the experiment was repeated in cholesterol-fed rabbits at the three-week timepoint, which showed comparable increases in plaque progression.

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Figure 1: Representative cellular distributions from fluorescence- activated cell sorting (FACS) analyses performed at week 3.
Figure 2: Quantitative assessment of cross-sectional plaque formation.
Figure 3: Representative photomicrographs 3 wk after treatment.
Figure 4: Cross-sectional endothelial density and macrophage infiltration.
Figure 5: Quantitative assessment of cross-sectional plaque formation in rabbit model.

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Correspondence to Michael D. Dake.

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Celletti, F., Waugh, J., Amabile, P. et al. Vascular endothelial growth factor enhances atherosclerotic plaque progression. Nat Med 7, 425–429 (2001). https://doi.org/10.1038/86490

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