title: Vascular endothelial growth factor (VEGF)-eluting stents: in vivo effects on thrombosis, endothelialization and intimal hyperplasia.
abstract: Local drug delivery by stent can reduce in-stent restenosis. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen. After stenting, the arterial wall is almost denuded of endothelium. This loss of endothelium contributes to the smooth muscle cell (SMC) proliferation seen in restenosis, since the endothelium actively inhibits SMC hyperplasia. Over time, the endothelium recovers and SMC hyperplasia is arrested. The capacity of VEGF-coated stents to accelerate re-endothelialization, and to therefore reduce restenosis and thrombosis, was tested in this study. Radiolabeled VEGF was absorbed onto stents and released over nine days in an in vitro perfusion circuit. VEGF-coated stents were deployed in arterial segments to study local tissue release. A New Zealand White rabbit iliac artery model for stent implantation was used. Re-endothelialization and thrombosis were assessed after seven days. Further animals were examined 28 days post-procedure for in-stent restenosis. Stented vessels were resin-embedded, sectioned and stained. Intimal thickening was calculated using computerized morphometry. In vitro, the stents released 80% of the initial load over nine days. At seven days, thrombus was significantly reduced (12.5 mg for controls versus 0 mg for VEGF; p = 0.014). No beneficial effect was seen on endothelialization, nor on intimal hyperplasia. Neointimal area was 2.2   0.9 mm2 for controls versus 2.4   1.8 mm2 for VEGF (p = 0.8). These VEGF-eluting stents do not accelerate re-endothelialization or inhibit restenosis. Stent thrombosis appears to be reduced, which may make these stents less thrombogenic and be valuable in higher-risk cases.
authors.affiliation: University of Leicester, Cardiology Clinical Sciences, Leicester, United Kingdom. b.n.swanson@talk21.com
authors.forename: Neil
authors.initials: N
authors.lastname: Swanson
authors.forename: Kai
authors.initials: K
authors.lastname: Hogrefe
authors.forename: Qamar
authors.initials: Q
authors.lastname: Javed
authors.forename: Nadim
authors.initials: N
authors.lastname: Malik
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Gershlick
mesh_terms: D000818:Animals; D019917:Blood Vessel Prosthesis Implantation; D020099:Coated Materials, Biocompatible / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000473:pathology / Q000601:surgery; D006083:Graft Occlusion, Vascular / Q000209:etiology / Q000401:mortality; D006965:Hyperplasia / Q000401:mortality / Q000628:therapy; D008297:Male; D011817:Rabbits; D015607:Stents; D013927:Thrombosis / Q000401:mortality / Q000628:therapy; D013997:Time Factors; D016896:Treatment Outcome; D017539:Tunica Intima / Q000473:pathology / Q000601:surgery; D042461:Vascular Endothelial Growth Factor A / Q000627:therapeutic use*
chemical_list: D020099:Coated Materials, Biocompatible; D042461:Vascular Endothelial Growth Factor A