Laitinen M, Ylä-Herttuala S
A.I. Virtanen Institute, University of Kuopio, Finland.
Curr Opin Lipidol. 1998 Oct;9(5):465-9. doi: 10.1097/00041433-199810000-00011.
Local gene transfer into the vascular wall offers a promising alternative to treat atherosclerosis-related diseases at cellular and molecular levels. Blood vessels are among the easiest targets for gene therapy because of novel percutaneous, catheter-based treatment methods. On the other hand, gene transfer to the artery wall can also be accomplished from adventitia, and in some situations intramuscular gene delivery is also a possibility. In most conditions, such as postangioplasty restenosis, only a temporary expression of the transfected gene will be required. Promising therapeutic effects have been obtained in animal models of restenosis with the transfer of genes for vascular endothelial growth factor, fibroblast growth factor, thymidine kinase, p53, bcl-x, nitric oxide synthase and retinoblastoma. Also, growth arrest homeobox gene and antisense oligonucleotides against transcription factors or cell cycle regulatory proteins have produced beneficial therapeutic effects. Angiogenesis is an emerging new target for gene therapy of ischemic diseases. In addition, hyperlipoproteinemias may be improved by transferring functional lipoprotein-receptor genes into hepatocytes of affected individuals. First experiences of gene transfer methods in the human vascular system have been reported. However, further studies regarding gene delivery methods, vectors and safety of the procedures are needed before a full therapeutic potential of gene therapy in vascular diseases can be evaluated.
将基因局部导入血管壁为在细胞和分子水平治疗动脉粥样硬化相关疾病提供了一种有前景的替代方法。由于新颖的经皮导管治疗方法，血管是基因治疗最容易的靶点之一。另一方面，基因也可以从外膜导入动脉壁，在某些情况下，肌内基因递送也是可能的。在大多数情况下，如血管成形术后再狭窄，只需要转染基因的临时表达。通过转移血管内皮生长因子、成纤维细胞生长因子、胸苷激酶、p53、bcl-x、一氧化氮合酶和视网膜母细胞瘤等基因，在再狭窄动物模型中已获得了有前景的治疗效果。此外，生长停滞同源框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也产生了有益的治疗效果。血管生成是缺血性疾病基因治疗的一个新兴新靶点。另外，通过将功能性脂蛋白受体基因导入受影响个体的肝细胞，可改善高脂蛋白血症。已经报道了基因转移方法在人体血管系统中的初步经验。然而，在评估基因治疗在血管疾病中的全部治疗潜力之前，还需要对基因递送方法、载体和该程序的安全性进行进一步研究。
