Enhanced Inhibition of Neointimal Hyperplasia by Genetically Engineered Endothelial Progenitor Cells

DOI Web Site 被引用文献13件
  • Deling Kong
    From the Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass (D.K., L.G.M., A.A.M., L.Z., M.L.-I., M.A.P., C.C.L., R.E.P., V.J.D.), and the Department of Physiology, Queen’s University, Kingston, Ontario, Canada (L.G.M.). Dr Kong is currently at the College of Science, Nankai University, People’s Republic of China.
  • Luis G. Melo
    From the Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass (D.K., L.G.M., A.A.M., L.Z., M.L.-I., M.A.P., C.C.L., R.E.P., V.J.D.), and the Department of Physiology, Queen’s University, Kingston, Ontario, Canada (L.G.M.). Dr Kong is currently at the College of Science, Nankai University, People’s Republic of China.
  • Abeel A. Mangi
    From the Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass (D.K., L.G.M., A.A.M., L.Z., M.L.-I., M.A.P., C.C.L., R.E.P., V.J.D.), and the Department of Physiology, Queen’s University, Kingston, Ontario, Canada (L.G.M.). Dr Kong is currently at the College of Science, Nankai University, People’s Republic of China.
  • Lunan Zhang
    From the Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass (D.K., L.G.M., A.A.M., L.Z., M.L.-I., M.A.P., C.C.L., R.E.P., V.J.D.), and the Department of Physiology, Queen’s University, Kingston, Ontario, Canada (L.G.M.). Dr Kong is currently at the College of Science, Nankai University, People’s Republic of China.
  • Marco Lopez-Ilasaca
    From the Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass (D.K., L.G.M., A.A.M., L.Z., M.L.-I., M.A.P., C.C.L., R.E.P., V.J.D.), and the Department of Physiology, Queen’s University, Kingston, Ontario, Canada (L.G.M.). Dr Kong is currently at the College of Science, Nankai University, People’s Republic of China.
  • Mark A. Perrella
    From the Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass (D.K., L.G.M., A.A.M., L.Z., M.L.-I., M.A.P., C.C.L., R.E.P., V.J.D.), and the Department of Physiology, Queen’s University, Kingston, Ontario, Canada (L.G.M.). Dr Kong is currently at the College of Science, Nankai University, People’s Republic of China.
  • Chong C. Liew
    From the Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass (D.K., L.G.M., A.A.M., L.Z., M.L.-I., M.A.P., C.C.L., R.E.P., V.J.D.), and the Department of Physiology, Queen’s University, Kingston, Ontario, Canada (L.G.M.). Dr Kong is currently at the College of Science, Nankai University, People’s Republic of China.
  • Richard E. Pratt
    From the Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass (D.K., L.G.M., A.A.M., L.Z., M.L.-I., M.A.P., C.C.L., R.E.P., V.J.D.), and the Department of Physiology, Queen’s University, Kingston, Ontario, Canada (L.G.M.). Dr Kong is currently at the College of Science, Nankai University, People’s Republic of China.
  • Victor J. Dzau
    From the Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass (D.K., L.G.M., A.A.M., L.Z., M.L.-I., M.A.P., C.C.L., R.E.P., V.J.D.), and the Department of Physiology, Queen’s University, Kingston, Ontario, Canada (L.G.M.). Dr Kong is currently at the College of Science, Nankai University, People’s Republic of China.

抄録

<jats:p> <jats:bold> <jats:italic>Background—</jats:italic> </jats:bold> Circulating endothelial progenitor cells (EPCs) have been reported previously. In this study, we examined the hypothesis that overexpression of vasculoprotective gene endothelial nitric oxide synthase (eNOS) and heme oxygenase-1 (HO-1) in EPCs enhances their ability to inhibit neointimal hyperplasia. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods and Results—</jats:italic> </jats:bold> EPCs were isolated from rabbit peripheral blood, expanded in culture, and transduced with pseudotyped retroviral vectors expressing human eNOS (eNOS-EPCs), HO-1 (HO-1-EPCs), or green fluorescent protein (GFP-EPCs). Transduction efficiency of EPCs ex vivo was >90%. Four groups of rabbits (n=5 to 6 per group) were subjected to balloon angioplasty of the common carotid artery. Immediately after injury, ≈5×10 <jats:sup>6</jats:sup> autologous eNOS-EPCs or HO-1-EPCs were transplanted into the injured vessel. Control animals received an equivalent number of GFP-EPCs or Ringer’s saline. Two weeks after transplantation, eNOS and HO-1 transgene transcripts and proteins were detected in the transduced rabbit vessels. Endothelialization was enhanced in the EPC-transplanted vessels independently of gene transfer. Neointimal thickening was significantly reduced in the GFP-EPC-treated vessels relative to the saline control. Neointima size was further reduced in vessels treated with eNOS-EPCs. Surprisingly, no additional reduction was seen in vessels treated with HO-1-EPCs relative to GFP-EPCs. Thrombosis occurred in ≈50% of the saline-treated vessels but was virtually absent in all EPC-transplanted vessels. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusions—</jats:italic> </jats:bold> We conclude that transplantation of autologous EPCs overexpressing eNOS in injured vessels enhances the vasculoprotective properties of the reconstituted endothelium, leading to inhibition of neointimal hyperplasia. This cell-based gene therapy strategy may be useful in treatment of vascular disease. </jats:p>

収録刊行物

  • Circulation

    Circulation 109 (14), 1769-1775, 2004-04-13

    Ovid Technologies (Wolters Kluwer Health)

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