Laitinen M, Ylä-Herttuala S
A.I. Virtanen Institute, University of Kuopio, Finland.
Pharmacol Res. 1998 Apr;37(4):251-4. doi: 10.1006/phrs.1998.0296.
Vascular gene transfer offers a promising alternative for the treatment of cardiovascular diseases. Blood vessels are among the easiest targets for gene therapy and in most conditions only a temporary expression of the transfected gene will be required to achieve a beneficial biological effect. Adenoviruses lead to most efficient transgene expression in arterial wall. Depending on the treatment requirements, gene transfer to the artery wall can be accomplished both from lumen and from adventitia. Promising therapeutic effects have been obtained in animal models of restenosis with the transfer of vascular endothelial growth factor (VEGF), nitric oxide synthase, thymidine kinase, retinoblastoma, growth arrest homeobox gene and antisense oligonucleotides against transcription factors or cell cycle regulatory proteins. First experiences of VEGF gene transfer to human peripheral arteries have also been reported. However, further studies regarding gene transfer techniques, vectors and safety of the procedures are needed before a full therapeutic potential of gene therapy in vascular diseases can be evaluated.
血管基因转移为心血管疾病的治疗提供了一种有前景的替代方法。血管是基因治疗最容易的靶标之一，在大多数情况下，仅需转染基因的短暂表达就能产生有益的生物学效应。腺病毒能使动脉壁中的转基因表达效率最高。根据治疗需求，可通过管腔和外膜两种途径将基因转移至动脉壁。在再狭窄动物模型中，通过转移血管内皮生长因子（VEGF）、一氧化氮合酶、胸苷激酶、视网膜母细胞瘤、生长停滞同源盒基因以及针对转录因子或细胞周期调节蛋白的反义寡核苷酸，已获得了有前景的治疗效果。也有关于将VEGF基因转移至人体外周动脉的初步经验报道。然而，在能够评估基因治疗在血管疾病中的全部治疗潜力之前，还需要对基因转移技术、载体及操作安全性进行进一步研究。
