Vascular endothelium has a local anti-adenovirus vector system and glucocorticoid optimizes its gene transduction
Vascular endothelium has a local anti-adenovirus vector system and glucocorticoid optimizes its gene transduction
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DOI：
10.1161/01.atv.0000174130.75958.b7
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发表时间：
2005-09-01
影响因子：
8.7
通讯作者：
Ozaki, H
中科院分区：
文献类型：
--
作者：
Murata, T;Hori, M;Ozaki, H
目的-尽管腺病毒是血管研究和治疗的有力工具，但感染后的内皮损伤已有报道。我们研究了这种损伤的机制和地塞米松（DEX）对基因转移到血管内皮细胞的影响。方法和结果-β-半乳糖苷酶基因编码腺病毒载体（β-gal-Ad）（7.5 × 10（8）空斑形成单位/mL）转导β-gal进入兔器官培养的肺内皮，随后细胞凋亡和内皮依赖性舒张（EDR）受损。β-gal-Ad感染的内皮细胞表达促炎基因mRNA，抑制内皮型一氧化氮合酶（eNOS）mRNA的表达。DEX治疗显著增加了内皮细胞中β-gal蛋白的表达，减弱了β-gal-Ad诱导的细胞凋亡，并防止了EDR的损害。DEX还能抑制促炎基因mRNA的表达，恢复内皮细胞eNOS mRNA的表达。此外，我们证实了DEX在内皮细胞系（体外）和大鼠股动脉（在体内）experiments.Conclusion的有益效果-这些结果表明，腺病毒载体诱导宿主免疫反应和血管内皮细胞凋亡。DEX是一种有效的工具，可以防止Ad诱导的内皮损伤，并在体外和体内实验中在蛋白翻译水平上优化腺病毒载体的基因表达效率。
Objective - Although adenovirus is a powerful tool for vascular research and therapy, endothelial impairment after infection has been reported. We investigated the mechanisms of this impairment and the effect of dexamethasone (DEX) on gene transfer into the vascular endothelial cells.Methods and Results - beta-Galactosidase gene encoding adenovirus vector (beta-gal-Ad) (7.5 x 10(8) plaque-forming units/mL) transduced beta-gal into the rabbit organ - cultured pulmonary endothelium, followed by an apoptosis and an impairment of endothelium-dependent relaxation (EDR). Endothelial cell infected by beta-gal-Ad expressed proinflammatory genes mRNAs and suppressed endothelial nitric oxide synthase ( eNOS) mRNA. Treatment with DEX dramatically increased beta-gal protein expression in the endothelium, attenuated beta-gal-Ad-induced apoptosis, and prevented the impairment of EDR. DEX also suppressed the mRNAs expressions of proinflammatory genes and recovered eNOS mRNA expression in organ-cultured vascular endothelium. In addition, we confirmed the DEX's beneficial effects in an endothelial cell line ( in vitro) and rat femoral artery ( in vivo) experiments.Conclusion - These results suggest that adenovirus vector induces host-immune responses and apoptosis in vascular endothelial cells. DEX is found to be a useful and potent tool to prevent the Ad-induced impairments of the endothelium and to optimize gene expression efficiency by adenovirus vector at the protein translation level in both in vitro and in vivo experiments.