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