title: Passivation of metallic stents after arterial gene transfer of phVEGF165 inhibits thrombus formation and intimal thickening.
abstract: OBJECTIVE
  This study sought to test the hypothesis that direct gene transfer of an endothelial cell mitogen could passivate metallic stents by accelerating endothelialization of the prosthesis.
  
  
  BACKGROUND
  Thrombosis and restenosis comprise the principal clinical manifestations of compromised biocompatibility of endovascular stents. Previous studies have demonstrated that endothelial recovery at sites of balloon injury is a critical determinant of consequent intimal thickening and mural thrombus. We therefore investigated the potential for an endothelial cell mitogen delivered as plasmid DNA to optimize stent biocompatibility.
  
  
  METHODS
  Naked plasmid DNA encoding vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) (phVEGF165) was delivered locally using a hydrogel-coated balloon angioplasty catheter to 16 rabbit iliac arteries in which metallic stents had been placed at the site of balloon injury; the contralateral iliac artery of each rabbit was balloon injured and stented but not transfected.
  
  
  RESULTS
  Stent endothelialization was accelerated by phVEGF165 gene transfer (87.38 +/- 5.06% vs. 33.13 +/- 9.73% [mean +/- SEM] of the planimetered stent surface in the treated vs. contralateral limb, p = 0.005). This was associated with a significant reduction in mural thrombus (3.7 +/- 2.4% vs. 32.7 +/- 9.7%, p = 0.01) at day 7 and intimal thickening (maximal intimal area 0.61 +/- 0.09 vs. 1.44 +/- 0.12 mm2, p < 0.0001) at day 28. No benefit was observed from pCMV-luciferase in 14 similarly instrumented control rabbits.
  
  
  CONCLUSIONS
  These findings indicate that arterial gene transfer of naked plasmid DNA encoding for an endothelial cell mitogen may successfully passivate endovascular stents by accelerating stent endothelialization, thereby reducing in-stent thrombus and obstruction due to intimal thickening.
authors.affiliation: Department of Medicine, (Cardiology), St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02135, USA.
authors.forename: E
authors.initials: E
authors.lastname: Van Belle
authors.forename: F O
authors.initials: FO
authors.lastname: Tio
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.forename: L
authors.initials: L
authors.lastname: Maillard
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.forename: M
authors.initials: M
authors.lastname: Kearney
authors.forename: J M
authors.initials: JM
authors.lastname: Isner
mesh_terms: D000800:Angioplasty, Balloon; D000818:Animals; D018076:DNA, Complementary / Q000008:administration & dosage; D016228:Endothelial Growth Factors / Q000008:administration & dosage* / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D018014:Gene Transfer Techniques; D007083:Iliac Artery / Q000293:injuries; D008222:Lymphokines / Q000008:administration & dosage* / Q000235:genetics; D011817:Rabbits; D015607:Stents; D013927:Thrombosis / Q000517:prevention & control*; D017539:Tunica Intima / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D018076:DNA, Complementary; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors