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Interact Cardiovasc Thorac Surg · Jul 2015
Early growth response gene-1 decoy oligonucleotides inhibit vascular smooth muscle cell proliferation and neointimal hyperplasia of autogenous vein graft in rabbits.
- Xisheng Wang, Yunqing Mei, Qiang Ji, Jing Feng, Jianzhi Cai, and Shiliang Xie.
- Department of Thoracic Cardiovascular Surgery, Tongji Hospital of Tongji University, Shanghai, China.
- Interact Cardiovasc Thorac Surg. 2015 Jul 1; 21 (1): 50-4.
ObjectivesThe excess proliferation of vascular smooth muscle cells (VSMCs) and the development of intimal hyperplasia is a hallmark of vein graft failure. This study aimed to verify that a single intraoperative transfection of early growth response gene-1 (Egr-1) decoy oligonucleotide (ODN) can suppress vein graft proliferation of VSMCs and intimal hyperplasia.MethodsIn a rabbit model, jugular veins were treated with Egr-1 decoy ODN, scrambled decoy ODN, Fugene6, or were left untreated, then grafted to the carotid artery. The vein graft samples were obtained 48 h, 1, 2 or 3 weeks after surgery. The thickness of the intima and intima/media ratio in the grafts was analysed by haematoxylin-eosin (HE) staining. The expression of the Egr-1 decoy ODN transfected in the vein was analysed using fluorescent microscopy. Egr-1 mRNA was measured using reverse transcription-polymerase chain reaction. The expression of Egr-1 protein was analysed by Western blot and immunohistochemistry.ResultsTransfection efficiency of the ODN was confirmed by 4', 6-diamidino-2-phenylindole staining. In the grafts treated with Egr-1 decoy ODN, our study achieved statistically significant inhibition of intimal hyperplasia by ∼58% at 3 weeks. Transfection of Egr-1 decoy ODNs decreased the protein expression of Egr-1 and Egr-1 mRNA.ConclusionsWe confirmed that gene therapy using in vivo transfection of an Egr-1 decoy ODN significantly inhibits proliferation of VSMC and intimal hyperplasia of vein grafts in a rabbit model.© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
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