Inhibition of plaque neovascularization and intimal hyperplasia by specific targeting vascular endothelial growth factor with bevacizumab-eluting stent: An experimental study

• Published in: Atherosclerosis 2007-12, Vol.195 (2), p.269-276
• Main Authors: Stefanadis, Christodoulos, Toutouzas, Konstantinos, Stefanadi, Elli, Lazaris, Andreas, Patsouris, Efstratios, Kipshidze, Nicholas
• Format: Article
• Language: English
• Subjects: Angiogenesis; Angiogenesis Inhibitors - pharmacology; Animals; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal, Humanized; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Bevacizumab; Biological and medical sciences; Blood and lymphatic vessels; Blood vessels and receptors; Cardiology. Vascular system; Cardiovascular; Disease Models, Animal; Drug-Eluting Stents; Endothelial Cells - drug effects; Endothelial Cells - immunology; Fundamental and applied biological sciences. Psychology; Iliac Artery - drug effects; Iliac Artery - pathology; Inflammation; Medical sciences; Neovascularization, Pathologic - prevention & control; Rabbits; Stents; Tunica Intima - drug effects; Tunica Intima - pathology; Vascular Endothelial Growth Factor A - drug effects; Vertebrates: cardiovascular system; Vessels
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2006.12.034

Abstract Neovascularization is associated with destabilization of atheromatic plaques. Increased expression of vascular endothelial growth factor (VEGF) is important in the process of neovascularization. We assessed the effect of bevacizumab, a monoclonal antibody specific for VEGF, on neovascularization. We used 12 New Zealand rabbits under atherogenic diet for 3 weeks. We immersed a phosphorycholine coated stent into a solution of 4 ml bevacizumab according to previous studies. Twelve eluting stents and 12 non-eluting stents were implanted in the middle segment of the rabbit's iliac arteries. Follow-up angiography was performed at 4 weeks and tissues were obtained for histological analysis. The procedure of stent loading with bevacizumab and stent implantation was successful. There was no difference in angiographic measurements before, after implantation and at follow-up between the two groups. mean neointimal thickness (0.09 ± 0.02 versus 0.12 ± 0.02 mm, p < 0.01), and mean neointimal area (1.08 ± 0.09 versus 1.20 ± 0.12 mm2 , p < 0.01) were less in the bevacizumab treated segments. bevacizumab-treated arterial segments demonstrated significantly decreased microvessel density compared with the control group (1.69 ± 0.06 CI: 1.65–1.73 versus 15.68 ± 0.56 CI: 15.32–16.04 vessels per mm2 , p < 0.001) and vegf expression was decreased in the media and adventitia of bevacizumab group. Endothelialization, inflammation and injury scores were similar between the two groups. These results suggest that bevacizumab-eluting stent implantation in rabbit iliac arteries is safe, and inhibits neovascularization without affecting the endothelialization.