Department of Bioengineering, College of Engineering, Hanyang University, Seoul 133-791, Republic of Korea.
Adv Drug Deliv Rev. 2011 Jul 18;63(8):678-87. doi: 10.1016/j.addr.2011.01.003. Epub 2011 Jan 15.
Ischemic heart diseases are caused by narrowed coronary arteries that decrease the blood supply to the myocardium. In the ischemic myocardium, hypoxia-responsive genes are up-regulated by hypoxia-inducible factor-1 (HIF-1). Gene therapy for ischemic heart diseases uses genes encoding angiogenic growth factors and anti-apoptotic proteins as therapeutic genes. These genes increase blood supply into the myocardium by angiogenesis and protect cardiomyocytes from cell death. However, non-specific expression of these genes in normal tissues may be harmful, since growth factors and anti-apoptotic proteins may induce tumor growth. Therefore, tight gene regulation is required to limit gene expression to ischemic tissues, to avoid unwanted side effects. For this purpose, various gene expression strategies have been developed for ischemic-specific gene expression. Transcriptional, post-transcriptional, and post-translational regulatory strategies have been developed and evaluated in ischemic heart disease animal models. The regulatory systems can limit therapeutic gene expression to ischemic tissues and increase the efficiency of gene therapy. In this review, recent progresses in ischemic-specific gene expression systems are presented, and their applications to ischemic heart diseases are discussed.
缺血性心脏病是由冠状动脉狭窄引起的，这会减少心肌的血液供应。在缺血性心肌中，缺氧反应基因被缺氧诱导因子-1（HIF-1）上调。缺血性心脏病的基因治疗使用编码血管生成生长因子和抗细胞凋亡蛋白的基因作为治疗基因。这些基因通过血管生成增加心肌的血液供应，并保护心肌细胞免受细胞死亡。然而，这些基因在正常组织中的非特异性表达可能是有害的，因为生长因子和抗细胞凋亡蛋白可能会诱导肿瘤生长。因此，需要严格的基因调控来将基因表达限制在缺血组织中，以避免不必要的副作用。为此，已经开发了各种基因表达策略来实现缺血组织特异性基因表达。已经开发并评估了转录、转录后和翻译后调控策略在缺血性心脏病动物模型中的应用。这些调控系统可以将治疗基因的表达限制在缺血组织中，并提高基因治疗的效率。在这篇综述中，介绍了缺血组织特异性基因表达系统的最新进展，并讨论了它们在缺血性心脏病中的应用。
