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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Kong, D; Melo, LG; Mangi, AA; Zhang, L; Lopez-Ilasaca, M; Perrella, MA; Liew, CC; Pratt, RE; Dzau, VJ

Published Date

  • April 13, 2004

Published In

Volume / Issue

  • 109 / 14

Start / End Page

  • 1769 - 1775

PubMed ID

  • 15066951

Electronic International Standard Serial Number (EISSN)

  • 1524-4539

Digital Object Identifier (DOI)

  • 10.1161/01.CIR.0000121732.85572.6F


  • eng

Conference Location

  • United States