Gene therapy for arterial aneurysm

目的：血管内治疗动脉瘤是安全有效的，但与手术治疗结果相比，疾病复发频繁。本研究的目的是确定重组腺病毒将基因转移到血管壁的效果。方法与结果：首先用体外编码血管内皮生长因子（VEGF）、血小板衍生生长因子（PDGF）、碱性成纤维细胞生长因子（bFGF）和外泌atpase的腺病毒载体感染兔主动脉血管平滑肌细胞。基因转移后2天开始检测到重组蛋白，并在基因转移后至少持续10天。接下来，我们研究了重组腺病毒的局部基因转移是否能在损伤动脉中表达蛋白。暴露兔颈总动脉，并在1.5 cm的距离上进行暂时结扎分离。将31号针头插入节段。然后用0.1 ml含重组腺病毒的生理盐水填充切片30分钟。基因转移5天后，用单克隆抗体对感染动脉段进行免疫染色。在本研究中，蛋白质在重组腺病毒感染的动脉内侧SMCs中广泛表达。基因转移后3天开始检测到重组蛋白，并持续存在至少7天。腺病毒介导的损伤动脉中蛋白的局部表达可能预防动脉疾病

OBJECTIVE : Endovascular treatment of arterial aneurysm is safe and effective, but recurrence of disease is frequent compared with results with surgery. The purpose of this study was to determine the effects of gene transfer to vascular wall by recombinant adenovirus. METHODS and RESULTS : At first, vascular smooth muscle cells from rabbit aortic arteries were infected with adenovirus vector encoding vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF) and ecto-ATPDase in vitro. Recombinant proteins were detected from 2 days after gene transfer, and persisted for at least 10 days after gene transfer. We next investigated whether the local gene transfer by recombinant adenovirus could express proteins in injured arteries. The common carotid arteries of the rabbit were exposed and isolated by temporary ligation at a distance of 1.5 cm. A 31-gauge needle was inserted into the segment. Thereafter, the segment was filled with 0.1 ml of saline containing recombinant adenoviruses for 30 min. Five days after gene transfer, infected arterial segments were immunostained with the monoclonal antibody. In this study, proteins were broadly expressed in medial SMCs of arteries infected with recombinant adenovirus. Recombinant proteins were detected from 3 days after gene transfer, and persisted for at least 7 days after gene transfer CONCLUSION ; The adenovirus-mediated local expression of proteins in injured arteries might prevent arterial diseases