Overexpression of vascular endothelial growth factor in restenoticabdominal aorta of rabbits

Objective To investigate the expression of vascular endothelial growth factor (VEGF) in the wall of normal and restenotic abdominal aorta of rabbits. Methods Restenotic model was developed by balloon injured abdominal aorta in eight male New Zealand White rabbits fed with a 2.0%cholesterol diet beginning two weeks before operation and continuing four weeks after procedure. At the end of 4 weeks after injury, the animals underwent total body perfusion fixation. Then, the abdominal aorta from iliac artery root to the diaphragm was harvested and post fixed in 10%neutral formalin for 16 hours. Eight male animals fed with general diet were used for a normal control. The VEGF protein level in normal and restenotic abdominal aorta of rabbits was studied by means of immunohistochemistry. Results VEGF protein was detected in 5 (62.5%) of 8 normal abdominal aorta, 3 showed faint staining, and the remaining 2 showed moderate VEGF expression. VEGF expression at the protein level was identified in all 8 restenotic specimens, 2 showed faint staining, 4 showed moderate staining, and the remaining 2 showed strong VEGF expression. In contrast to normal vessels, VEGF in restenotic specimens was distinctly expressed at sites that contained clustered macrophages and proliferating smooth muscle cells as well as endothelial cells. VEGF immunostaining was more extensive in restenotic specimens (2.00±0.76) than in normal vessels (0.82±0.83, P< 0.01). Microvessels were found in 7 of the 8 restenotic lesions, but only one lesion showed VEGF staining in endothelial cells of the microvessels. Conclusion VEGF expression is consistently more intense in sections of restenotic abdominal aorta than in those of normal abdominal aorta. The VEGF expressed by the smooth muscle cells and foamy macrophages in the restenotic arteries may act as a local and endogenous regulator of endothelial cell functions, including maintenance and repair of luminal endothelium, and formation of intimal neovascularization.