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 / 中国胸心血管外科临床杂志

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.