Inhibition of plaque neovascularization and intimal hyperplasia by specific targeting vascular endothelial growth factor with bevacizumab-eluting stent: an experimental study.
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 mm(2), 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 mm(2), 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.
Stefanadis
Christodoulos
C
First Department of Cardiology, Hippokration Hospital, Athens Medical School, 9 Tepeleniou Str. 15452, Paleo Psychico, Athens, Greece. chstefan@med.uoa.gr
Toutouzas
Konstantinos
K
Stefanadi
Elli
E
Lazaris
Andreas
A
Patsouris
Efstratios
E
Kipshidze
Nicholas
N
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D004195:Disease Models, Animal; D054855:Drug-Eluting Stents; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology; D007083:Iliac Artery / Q000187:drug effects / Q000473:pathology; D007249:Inflammation; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011817:Rabbits; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects*
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab