ABSTRACT
OBJECTIVES: This study was designed to evaluate the impact of recombinant human vascular endothelial growth factor165 (rhVEGF) on atherosclerotic plaque progression. BACKGROUND: Therapeutic angiogenesis represents a promising treatment for ischemic diseases. However, angiogenesis may impact atherosclerosis. METHODS: Albumin or rhVEGF was administered by a single intramuscular injection (2 microg/kg body weight) to New Zealand White rabbits fed with a 0.25% cholesterol diet beginning three weeks before therapy. Subsets of rabbits from each group underwent perfusion-fixation and harvesting of the thoracic aorta for morphometric and immunohistochemical analyses at 7 or 21 days. RESULTS: The mean plaque area was 15.75+/-2.28% and 22.00+/-3.24% with VEGF and 0.67+/-0.22% and 1.17+/-0.34% with albumin at 7 and 21 days, respectively. The plaque circumference was 13.00+/-2.58% and 23.75+/-2.86% with VEGF and 2.50+/-0.65% and 6.25+/-1.88% with albumin at 7 and 21 days, respectively. The maximal plaque thickness was 0.11+/-0.002 and 0.15+/-0.007 mm with VEGF and 0.04+/-0.009 and 0.07+/-0.003 mm with albumin at 7 and 21 days, respectively. The endothelial density (reported as percent total plaque area) was 31.75+/-4.42% and 63.00+/-8.45% with VEGF and 7.75+/-1.65% and 12.75+/-1.93% with albumin at 7 and 21 days, respectively. The macrophage density was 4.5+/-0.86 and 19.25+/-1.54 with VEGF and 4.26+/-0.75 and 6.00+/-1.08 with albumin at 7 and 21 days, respectively. CONCLUSIONS: Recombinant human VEGF increases the rate and degree of atherosclerotic plaque formation in the thoracic aorta in a cholesterol-fed rabbit model.
Subject(s)
Aortic Diseases/pathology , Arteriosclerosis/pathology , Endothelial Growth Factors/adverse effects , Lymphokines/adverse effects , Protein Isoforms/adverse effects , Animals , Aorta, Thoracic , Arteriosclerosis/physiopathology , Disease Progression , Immunohistochemistry , Macrophages , Neovascularization, Physiologic , Rabbits , Recombinant Proteins , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth FactorsABSTRACT
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.
