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Enhanced inhibition of neointimal hyperplasia by genetically engineered endothelial progenitor cells.

Publication ,  Journal Article
Kong, D; Melo, LG; Mangi, AA; Zhang, L; Lopez-Ilasaca, M; Perrella, MA; Liew, CC; Pratt, RE; Dzau, VJ
Published in: Circulation
April 13, 2004

BACKGROUND: 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. METHODS AND RESULTS: 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, approximately 5x10(6) 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 approximately 50% of the saline-treated vessels but was virtually absent in all EPC-transplanted vessels. CONCLUSIONS: 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.

Duke Scholars

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Published In

Circulation

DOI

EISSN

1524-4539

Publication Date

April 13, 2004

Volume

109

Issue

14

Start / End Page

1769 / 1775

Location

United States

Related Subject Headings

  • Tunica Intima
  • Transduction, Genetic
  • Thrombosis
  • Retroviridae
  • Recombinant Fusion Proteins
  • Rabbits
  • RNA, Messenger
  • Nitric Oxide Synthase Type III
  • Nitric Oxide Synthase
  • Membrane Proteins
 

Citation

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Kong, D., Melo, L. G., Mangi, A. A., Zhang, L., Lopez-Ilasaca, M., Perrella, M. A., … Dzau, V. J. (2004). Enhanced inhibition of neointimal hyperplasia by genetically engineered endothelial progenitor cells. Circulation, 109(14), 1769–1775. https://doi.org/10.1161/01.CIR.0000121732.85572.6F
Kong, Deling, Luis G. Melo, Abeel A. Mangi, Lunan Zhang, Marco Lopez-Ilasaca, Mark A. Perrella, Chong C. Liew, Richard E. Pratt, and Victor J. Dzau. “Enhanced inhibition of neointimal hyperplasia by genetically engineered endothelial progenitor cells.Circulation 109, no. 14 (April 13, 2004): 1769–75. https://doi.org/10.1161/01.CIR.0000121732.85572.6F.
Kong D, Melo LG, Mangi AA, Zhang L, Lopez-Ilasaca M, Perrella MA, et al. Enhanced inhibition of neointimal hyperplasia by genetically engineered endothelial progenitor cells. Circulation. 2004 Apr 13;109(14):1769–75.
Kong, Deling, et al. “Enhanced inhibition of neointimal hyperplasia by genetically engineered endothelial progenitor cells.Circulation, vol. 109, no. 14, Apr. 2004, pp. 1769–75. Pubmed, doi:10.1161/01.CIR.0000121732.85572.6F.
Kong D, Melo LG, Mangi AA, Zhang L, Lopez-Ilasaca M, Perrella MA, Liew CC, Pratt RE, Dzau VJ. Enhanced inhibition of neointimal hyperplasia by genetically engineered endothelial progenitor cells. Circulation. 2004 Apr 13;109(14):1769–1775.

Published In

Circulation

DOI

EISSN

1524-4539

Publication Date

April 13, 2004

Volume

109

Issue

14

Start / End Page

1769 / 1775

Location

United States

Related Subject Headings

  • Tunica Intima
  • Transduction, Genetic
  • Thrombosis
  • Retroviridae
  • Recombinant Fusion Proteins
  • Rabbits
  • RNA, Messenger
  • Nitric Oxide Synthase Type III
  • Nitric Oxide Synthase
  • Membrane Proteins