Local Gene Transfer of phVEGF-2 Plasmid by Gene-Eluting Stents

  • Dirk H. Walter
    From the Department of Medicine (Cardiovascular Research), St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Mass; Department of Pathology (F.O.T), University of Texas, San Antonio, Tex; Center for Learning and Memory (P.K.), Massachusetts Institute of Technology, Cambridge, Mass; and Biocompatibles UK Limited (S.W., L.K., P.W.S.), Surrey, UK.
  • Manfred Cejna
    From the Department of Medicine (Cardiovascular Research), St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Mass; Department of Pathology (F.O.T), University of Texas, San Antonio, Tex; Center for Learning and Memory (P.K.), Massachusetts Institute of Technology, Cambridge, Mass; and Biocompatibles UK Limited (S.W., L.K., P.W.S.), Surrey, UK.
  • Larry Diaz-Sandoval
    From the Department of Medicine (Cardiovascular Research), St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Mass; Department of Pathology (F.O.T), University of Texas, San Antonio, Tex; Center for Learning and Memory (P.K.), Massachusetts Institute of Technology, Cambridge, Mass; and Biocompatibles UK Limited (S.W., L.K., P.W.S.), Surrey, UK.
  • Sean Willis
    From the Department of Medicine (Cardiovascular Research), St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Mass; Department of Pathology (F.O.T), University of Texas, San Antonio, Tex; Center for Learning and Memory (P.K.), Massachusetts Institute of Technology, Cambridge, Mass; and Biocompatibles UK Limited (S.W., L.K., P.W.S.), Surrey, UK.
  • Laura Kirkwood
    From the Department of Medicine (Cardiovascular Research), St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Mass; Department of Pathology (F.O.T), University of Texas, San Antonio, Tex; Center for Learning and Memory (P.K.), Massachusetts Institute of Technology, Cambridge, Mass; and Biocompatibles UK Limited (S.W., L.K., P.W.S.), Surrey, UK.
  • Peter W. Stratford
    From the Department of Medicine (Cardiovascular Research), St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Mass; Department of Pathology (F.O.T), University of Texas, San Antonio, Tex; Center for Learning and Memory (P.K.), Massachusetts Institute of Technology, Cambridge, Mass; and Biocompatibles UK Limited (S.W., L.K., P.W.S.), Surrey, UK.
  • Anne B. Tietz
    From the Department of Medicine (Cardiovascular Research), St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Mass; Department of Pathology (F.O.T), University of Texas, San Antonio, Tex; Center for Learning and Memory (P.K.), Massachusetts Institute of Technology, Cambridge, Mass; and Biocompatibles UK Limited (S.W., L.K., P.W.S.), Surrey, UK.
  • Rudolf Kirchmair
    From the Department of Medicine (Cardiovascular Research), St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Mass; Department of Pathology (F.O.T), University of Texas, San Antonio, Tex; Center for Learning and Memory (P.K.), Massachusetts Institute of Technology, Cambridge, Mass; and Biocompatibles UK Limited (S.W., L.K., P.W.S.), Surrey, UK.
  • Marcy Silver
    From the Department of Medicine (Cardiovascular Research), St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Mass; Department of Pathology (F.O.T), University of Texas, San Antonio, Tex; Center for Learning and Memory (P.K.), Massachusetts Institute of Technology, Cambridge, Mass; and Biocompatibles UK Limited (S.W., L.K., P.W.S.), Surrey, UK.
  • Cindy Curry
    From the Department of Medicine (Cardiovascular Research), St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Mass; Department of Pathology (F.O.T), University of Texas, San Antonio, Tex; Center for Learning and Memory (P.K.), Massachusetts Institute of Technology, Cambridge, Mass; and Biocompatibles UK Limited (S.W., L.K., P.W.S.), Surrey, UK.
  • Andrea Wecker
    From the Department of Medicine (Cardiovascular Research), St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Mass; Department of Pathology (F.O.T), University of Texas, San Antonio, Tex; Center for Learning and Memory (P.K.), Massachusetts Institute of Technology, Cambridge, Mass; and Biocompatibles UK Limited (S.W., L.K., P.W.S.), Surrey, UK.
  • Young-Sup Yoon
    From the Department of Medicine (Cardiovascular Research), St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Mass; Department of Pathology (F.O.T), University of Texas, San Antonio, Tex; Center for Learning and Memory (P.K.), Massachusetts Institute of Technology, Cambridge, Mass; and Biocompatibles UK Limited (S.W., L.K., P.W.S.), Surrey, UK.
  • Regina Heidenreich
    From the Department of Medicine (Cardiovascular Research), St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Mass; Department of Pathology (F.O.T), University of Texas, San Antonio, Tex; Center for Learning and Memory (P.K.), Massachusetts Institute of Technology, Cambridge, Mass; and Biocompatibles UK Limited (S.W., L.K., P.W.S.), Surrey, UK.
  • Allison Hanley
    From the Department of Medicine (Cardiovascular Research), St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Mass; Department of Pathology (F.O.T), University of Texas, San Antonio, Tex; Center for Learning and Memory (P.K.), Massachusetts Institute of Technology, Cambridge, Mass; and Biocompatibles UK Limited (S.W., L.K., P.W.S.), Surrey, UK.
  • Marianne Kearney
    From the Department of Medicine (Cardiovascular Research), St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Mass; Department of Pathology (F.O.T), University of Texas, San Antonio, Tex; Center for Learning and Memory (P.K.), Massachusetts Institute of Technology, Cambridge, Mass; and Biocompatibles UK Limited (S.W., L.K., P.W.S.), Surrey, UK.
  • Fermin O. Tio
    From the Department of Medicine (Cardiovascular Research), St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Mass; Department of Pathology (F.O.T), University of Texas, San Antonio, Tex; Center for Learning and Memory (P.K.), Massachusetts Institute of Technology, Cambridge, Mass; and Biocompatibles UK Limited (S.W., L.K., P.W.S.), Surrey, UK.
  • Patrik Kuenzler
    From the Department of Medicine (Cardiovascular Research), St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Mass; Department of Pathology (F.O.T), University of Texas, San Antonio, Tex; Center for Learning and Memory (P.K.), Massachusetts Institute of Technology, Cambridge, Mass; and Biocompatibles UK Limited (S.W., L.K., P.W.S.), Surrey, UK.
  • Jeffrey M. Isner
    From the Department of Medicine (Cardiovascular Research), St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Mass; Department of Pathology (F.O.T), University of Texas, San Antonio, Tex; Center for Learning and Memory (P.K.), Massachusetts Institute of Technology, Cambridge, Mass; and Biocompatibles UK Limited (S.W., L.K., P.W.S.), Surrey, UK.
  • Douglas W. Losordo
    From the Department of Medicine (Cardiovascular Research), St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Mass; Department of Pathology (F.O.T), University of Texas, San Antonio, Tex; Center for Learning and Memory (P.K.), Massachusetts Institute of Technology, Cambridge, Mass; and Biocompatibles UK Limited (S.W., L.K., P.W.S.), Surrey, UK.

書誌事項

タイトル別名
  • An Alternative Strategy for Inhibition of Restenosis

抄録

<jats:p> <jats:bold> <jats:italic>Background—</jats:italic> </jats:bold> 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. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods and Results—</jats:italic> </jats:bold> phVEGF 2-plasmid (100 or 200 μg 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%, <jats:italic>P</jats:italic> <0.01). At 3 months, intravascular ultrasound analysis revealed that lumen cross-sectional area (4.2±0.4 versus 2.27±0.3 mm <jats:sup>2</jats:sup> , <jats:italic>P</jats:italic> <0.001) was significantly greater and percent cross-sectional narrowing was significantly lower (23.4±6 versus 51.2±10, <jats:italic>P</jats:italic> <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. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusions—</jats:italic> </jats:bold> 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. </jats:p>

収録刊行物

  • Circulation

    Circulation 110 (1), 36-45, 2004-07-06

    Ovid Technologies (Wolters Kluwer Health)

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