Gene therapy for arterial aneurysm

目的：血管内治疗是一种安全有效的治疗方法，但与手术治疗相比，复发较多。本研究的目的是确定重组腺病毒对血管壁基因转移的效果。方法和结果：首先用携带血管内皮细胞生长因子(VEGF)、血小板衍生生长因子(PDGF)、碱性成纤维细胞生长因子(BFGF)和外源性ATPDase基因的腺病毒载体感染体外培养的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局部基因转移能否在损伤的动脉中表达蛋白质。暴露兔颈总动脉，在1.5 cm处临时结扎分离。一根31号的针被插入节段。此后，将含有重组腺病毒的0.1ml生理盐水填充到该片段中30分钟。基因转移5天后，用单抗对感染动脉节段进行免疫组织化学染色。在本研究中，重组腺病毒感染的动脉中膜细胞广泛表达蛋白质。结论：腺病毒介导的蛋白局部表达可预防动脉疾病的发生。

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