Journal
CIRCULATION
Volume 109, Issue 14, Pages 1769-1775Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.CIR.0000121732.85572.6F
Keywords
endothelium; cells; hyperplasia; gene therapy
Funding
- NHLBI NIH HHS [HL-35610, HL-073219, HL-072010, HL-058516] Funding Source: Medline
Ask authors/readers for more resources
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, approximate to 5 x 10(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 approximate to50% 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available