The Role of ex-vivo Gene Therapy of Vein Grafts with Egr-1 Decoy in the Suppression of Intimal Hyperplasia

被引：8

作者：

Peroulis, M. ^{[1
,2
]}

Kakisis, J. ^{[1
,2
]}

Kapelouzou, A. ^{[1
]}

Giagini, A. ^{[1
]}

Giaglis, S. ^{[1
]}

Mantziaras, G. ^{[1
]}

Kostomitsopoulos, N. ^{[1
]}

Karayannacos, P. ^{[1
]}

Macheras, A. ^{[2
]}

机构：

[1] Acad Athens, Ctr Expt Surg, Fdn Biomed Res, Athens, Greece

[2] Univ Athens, Sch Med, Dept Surg 3, Attikon Hosp, GR-11527 Athens, Greece

来源：

EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY | 2010年 / 40卷 / 02期

关键词：

Egr-1; Decoy; Gene therapy; Graft occlusion; Vascular; Intimal hyperplasia; Endothelial cells; NF-KAPPA-B; TRANSCRIPTION FACTOR DECOY; MUSCLE-CELL-PROLIFERATION; VASCULAR BYPASS GRAFTS; NEOINTIMAL HYPERPLASIA; HYPERCHOLESTEROLEMIC RABBITS; CONTROLLED-TRIAL; E2F DECOY; MODEL; INHIBITION;

D O I：

10.1016/j.ejvs.2010.04.013

中图分类号：

R61 [外科手术学];

学科分类号：

摘要：

Objectives: To test the hypothesis that vein graft intimal hyperplasia can be significantly suppressed by a single intra-operative transfection of the graft with a decoy oligonucleotide (ODN) binding the transcription factor Egr-1. Design: Experimental study. Materials and methods: Jugular vein to carotid artery interposition grafts in rabbits were treated with Egr-1 decoy, mutant decoy ODN, vehicle alone, using a non-distending pressure of 300 mmHg for 20 min, or were left untreated. All animals were fed a 2% cholesterol diet. The animals were sacrificed after 48 h, 6 weeks and 12 weeks. Paraffin-embedded vein sections were subjected to angiometric analysis. Results: Successful delivery of the ODN was confirmed by DAPI staining. Quantitative real-time PCR revealed a 60% decrease of the Egr-1 gene expression in the animals in which the Egr-1 decoy ODN was delivered. Cellular proliferation was also significantly decreased as indicated by the Ki-67 labelling index. An increase in intimal and medial thickness was found in all vein grafts. However, intimal thickness was significantly reduced in the grafts treated with Egr-1 decoy ODN, whereas luminal area was significantly increased. Conclusion: A single intra-operative pressure-mediated transfection of vein grafts with Egr-1 decoy ODN significantly suppresses intimal hyperplasia in a rabbit hypercholesterolaemic model. (C) 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

引用

页码：216 / 223

页数：8