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 microg/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.

Stimulation of vascularization of a subcutaneous scaffold applicable for pancreatic islet‐transplantation enhances immediate post‐transplant islet graft function but not long‐term normoglycemia

“…Their data and ours suggest that establishment of a stable vascular network is complex and might require several angiogenic factors to promote vessel sprouting and remodeling of the vascular network 38. This is supported by clinical studies demonstrating even detrimental effects after injections of a single growth factor 39, 40, 41…”

Development of Contrast Agents Targeted to Macrophage Scavenger Receptors for MRI of Vascular Inflammation

“…Moreover, the cell densities used for these studies is on the order of that found for macrophages in isolated human plaques, indicating that these imaging results will be applicable to the in vivo case. (52)(53)(54)(55)(56) There are number of examples in the literature of efficient cellular uptake of Gd(III) complexes using Gd-DOTA derived molecules (57)(58)(59)(60). More recent efforts have sought to maximize the load of Gd delivered per receptor by tethering carrier molecules to dendridic polymers containing high numbers of Gd(III)(61), uptake through the folate receptor has been demonstrated by this means as has avidin-biotin antibody-based targeting (59,62,63).…”

Vitamins C and E downregulate vascular VEGF and VEGFR-2 expression in apolipoprotein-E-deficient mice

“…Despite these functions, VEGF could also be considered a pro-atherogenic factor, because its administration increases the rate and degree of atherosclerotic plaque formation in apo-E/apo-B100 deficient mice and in hypercholesterolemic rabbits [8]. Moreover, VEGF has been found to be upregulated in human coronary atherosclerotic lesions but not in normal coronary segments [9].…”