Effect of human recombinant vascular endothelial growth factor165 on progression of atherosclerotic plaque

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 μg/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.