Mosaic adeno-associated virus-mediated gene transfer of calcitonin gene-related peptide for prevention of inflammatory mediator expression, macrophage infiltration and neointimal hyperplasia in an experimental rabbit vein graft model
10.7507/1007-4848.201604054
- VernacularTitle:降钙素基因相关肽转基因对移植静脉病的防治作用
- Author:
ZHANG Xiaoning
1
,
2
;
ZHUANG Jian
3
;
WU Hongsui
3
;
CHEN Zhihong
3
;
SU Jian
3
;
CHEN Shiliang
3
;
CHEN Jianguang
3
Author Information
1. 1. Department of Cardiovascular Surgery, Guangdong Academy of Medical Sciences, Guangdong General Hospital, Guangzhou, 510080, P.R.China
2. 2. Department of Cardiothoracic Surgery, Heze Traditional Chinese Medicine Hospital, Heze, 274000, Shandong, P.R.China
3. Department of Cardiovascular Surgery, Guangdong Academy of Medical Sciences, Guangdong General Hospital, Guangzhou, 510080, P.R.China
- Publication Type:Journal Article
- Keywords:
Vein graft disease;
calcitonin gene-related peptide;
gene therapy
- From:
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery
2017;24(11):880-885
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect and mechanism of calcitonin gene-related peptide (CGRP) on the prevention and treatment of transplant vein graft disease. Methods The 25 New Zealand white rabbits were divided into three groups: an experimental group [n=8, the rabbit jugular veins transfected with adeno-associated virus vector tipe 2/1 containing CGRP gene (AAV2/1-CGRP)], a carrier group [n=9, transfected with mosaic adeno-associated virus vector tipe 2/1 containing LacZ gene (AAV2/1-LacZ)] and a control group (n=8, saline) and then the cervical veins were implantated into the ipsilateral carotid artery by reverse end-side anastomosis. At 4 weeks after surgery, the pathology of the specimens, CD68 immunohistochemistry, in situ β-galactosidase staining were obtained. The expression of CGRP gene was detected by reverse transcription-polymerase chain reaction (RT-PCR). Monocyte chemoattractant protein-1(MCP- 1), tumour necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS) and matrix metalloproteinase-9 (MMP-9) were detected by real-time polymerase chain reaction (real-time PCR). Results The CGRP and LacZ gene expression was positive at postoperative 4 weeks. The intima/media ratio was significantly inhibited in the experimental group. Macrophage infiltration and expression of inflammatory mediators including MCP-1, TNF-α, iNOS and MMP-9 were also significantly inhibited in the experimental group. Conclusion Transfection of AAV2/1-CGRP inhibits inflammatory mediator expression, macrophage infiltration and neointimal hyperplasia in experimental vein graft disease.
