Gruchala Marcin, Roy Himadri, Bhardwaj Shalini, Ylä-Herttuala Seppo
Department of Molecular Medicine, A.I. Virtanen Institute, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland.
Curr Pharm Des. 2004;10(4):407-23. doi: 10.2174/1381612043453379.
Gene therapy is a rapidly evolving field of medicine, which potentially offers new treatments for cardiovascular diseases. With the use of gene transfer methods it is possible to modify somatic cells in blood vessels and myocardium to overexpress or inhibit pathologically important proteins and achieve therapeutic effects. Prevention of restenosis after vascular interventions such as percutanous coronary angioplasty (PTCA), percutanous peripheral angioplasty (PTA) or stent implantation, prevention of venous graft failures and therapeutic angiogenesis are the major aims of experimental studies and clinical gene therapy. The promise of gene therapy in the treatment of cardiovascular diseases remains high. Experimental studies have established the proof of principle that gene transfer to cardiovascular system can achieve therapeutic effects. First human clinical trials provided initial evidence of the feasibility and safety of the novel therapy. There are also first successful reports on the prevention of neointimal hyperplasia and promotion of therapeutic angiogenesis in clinical trials. However, there are still important questions regarding utility, efficiency and safety of gene therapy in the treatment of cardiovascular diseases. In this review we discuss the rapid progress in cardiovascular gene therapy, the development of delivery systems and vectors, most promising therapeutic genes and results of the recent human clinical trials.
基因治疗是医学领域中一个快速发展的领域，它有可能为心血管疾病提供新的治疗方法。通过使用基因转移方法，可以对血管和心肌中的体细胞进行修饰，使其过度表达或抑制具有病理重要性的蛋白质，从而达到治疗效果。预防血管介入治疗（如经皮冠状动脉腔内血管成形术（PTCA）、经皮外周血管成形术（PTA）或支架植入）后的再狭窄、预防静脉移植物失败以及治疗性血管生成是实验研究和临床基因治疗的主要目标。基因治疗在心血管疾病治疗中的前景依然广阔。实验研究已经确立了将基因转移到心血管系统可实现治疗效果的原理证明。首批人体临床试验为这种新型治疗方法的可行性和安全性提供了初步证据。在临床试验中也有关于预防内膜增生和促进治疗性血管生成的首批成功报道。然而，关于基因治疗在心血管疾病治疗中的实用性、有效性和安全性仍存在重要问题。在这篇综述中，我们将讨论心血管基因治疗的快速进展、递送系统和载体的发展、最有前景的治疗性基因以及近期人体临床试验的结果。
