title: Local gene transfer of phVEGF-2 plasmid by gene-eluting stents: an alternative strategy for inhibition of restenosis.
abstract: BACKGROUND
  Drug-eluting stents represent a useful strategy for the prevention of restenosis using various antiproliferative drugs. These strategies share the liability of impairing endothelial recovery, thereby altering the natural biology of the vessel wall and increasing the associated risk of stent thrombosis. Accordingly, we tested the hypothesis that local delivery via gene-eluting stent of naked plasmid DNA encoding for human vascular endothelial growth factor (VEGF)-2 could achieve similar reductions in neointima formation while accelerating, rather than inhibiting, reendothelialization.
  
  
  RESULTS
  phVEGF 2-plasmid (100 or 200 microg per stent)-coated BiodivYsio phosphorylcholine polymer stents versus uncoated stents were deployed in a randomized, blinded fashion in iliac arteries of 40 normocholesterolemic and 16 hypercholesterolemic rabbits. Reendothelialization was nearly complete in the VEGF stent group after 10 days and was significantly greater than in control stents (98.7+/-1% versus 79.0+/-6%, P<0.01). At 3 months, intravascular ultrasound analysis revealed that lumen cross-sectional area (4.2+/-0.4 versus 2.27+/-0.3 mm(2), P<0.001) was significantly greater and percent cross-sectional narrowing was significantly lower (23.4+/-6 versus 51.2+/-10, P<0.001) in VEGF stents compared with control stents implanted in hypercholesterolemic rabbits. Transgene expression was detectable in the vessel wall along with improved functional recovery of stented segments, resulting in a 2.4-fold increase in NO production.
  
  
  CONCLUSIONS
  Acceleration of reendothelialization via VEGF-2 gene-eluting stents provides an alternative treatment strategy for the prevention of restenosis. VEGF-2 gene-eluting stents may be considered as a stand-alone or combination therapy.
authors.affiliation: Department of Medicine, St Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Mass 02135, USA.
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Walter
authors.forename: Manfred
authors.initials: M
authors.lastname: Cejna
authors.forename: Larry
authors.initials: L
authors.lastname: Diaz-Sandoval
authors.forename: Sean
authors.initials: S
authors.lastname: Willis
authors.forename: Laura
authors.initials: L
authors.lastname: Kirkwood
authors.forename: Peter W
authors.initials: PW
authors.lastname: Stratford
authors.forename: Anne B
authors.initials: AB
authors.lastname: Tietz
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kirchmair
authors.forename: Marcy
authors.initials: M
authors.lastname: Silver
authors.forename: Cindy
authors.initials: C
authors.lastname: Curry
authors.forename: Andrea
authors.initials: A
authors.lastname: Wecker
authors.forename: Young-Sup
authors.initials: YS
authors.lastname: Yoon
authors.forename: Regina
authors.initials: R
authors.lastname: Heidenreich
authors.forename: Allison
authors.initials: A
authors.lastname: Hanley
authors.forename: Marianne
authors.initials: M
authors.lastname: Kearney
authors.forename: Fermin O
authors.initials: FO
authors.lastname: Tio
authors.forename: Patrik
authors.initials: P
authors.lastname: Kuenzler
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Isner
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Losordo
mesh_terms: D000818:Animals; D001157:Arterial Occlusive Diseases / Q000000981:diagnostic imaging / Q000473:pathology / Q000517:prevention & control*; D003131:Combined Modality Therapy; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D010957:Plasmids / Q000008:administration & dosage; D011817:Rabbits; D013234:Stem Cells / Q000166:cytology; D015607:Stents; D014463:Ultrasonography; D042442:Vascular Endothelial Growth Factors / Q000032:analysis / Q000235:genetics*
chemical_list: D042442:Vascular Endothelial Growth Factors; D009569:Nitric Oxide