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ȣ - 490027 98 |
| Intravascular Angiopoietin-1 Gene Plasmid and Bone Marrow Mononeuclear Cell Transfer Accelerates Reendothelialization in Balloon-denuded Rat Carotid Artery |
| 전남대학병원 순환기내과, 광주원광대학병원 순환기 내과 |
| 김원, 정명호, 임상엽, 이상록, 김계훈, 손일석, 박형욱, 김주한, , 안영근, 조정관, 박종춘, 강정채, 박옥규 |
BACKGROUND: Gene transfer to the vessel wall may provide new possibilities for the treatment of vascular disorders. Bone marrow derived mononeuclear cells (BMMNCs) have been shown to contribute to endothelial replacement after vascular injury. In this study, we analyzed the effects of human Angiopoietin-1 (pCAhAng-1) plasmid transfer with/without BMMNCs on neointima formation and reendothelialization after endothelial denudation in carotid artery of rats.
METHODS AND RESULTS: Carotid arteries of SD rats were balloon-denuded, and control vector (Group I), pCAhAng-1 gene plasmid (30ug) transfer (Group II) and pCAhAng-1 gene (30ug) and BMMNCs (6×105 cell) delivery (Group III) was performed by 30 minutes of local dwelling, immediately. Animals were euthanized 2 weeks after the gene/cell transfer, and intima/media ratio (I/M), reendothelialization index, histology, and cell proliferation were analyzed. A pCAhAng-1 gene transfer confirmed by Lac Z stain and RT-PCR on 3 days after transfer. Administered PKH-26 green labelled BMMNCs incorporate into vessel wall 8 day after balloon carotid injury by immunofluorescence stain. Two weeks after the gene/cell transfer, I/M in the group I was 0.81±0.16. pCAhAng-1 gene transfer reduced I/M to 0.30±0.09 (p=0.000 versus control) and pCAhAng-1 and BMMNCs transfer reduced I/M to 0.18±0.06 (p=0.000 versus control). The reendothelialization area by Evans Blue stain was 41.6±6.9% in control vector group, 75.9±5.9% in pCAhAng-1 (p=0.000 versus control), 82.3±4.3% in combination group (p=0.000 versus control). CD31 and Factor VIII stain showed was 41.±6.5% in control vector group, 72.5±11.1% in pCAhAng-1 (p=0.000 versus control), 86.4±5.7% in combination group (p=0.000 versus control), but no significant difference between the group II and group III.
CONCLUSIONS: These data demonstrated that transfer of pCAhAng-1 gene and BMMNCs delivery to balloon-injured arteries is associated with accelerated reendothelialization, reduced neointima formation. These finding may have implications for novel and practical combination therapies for vasculoprotective approach.
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