The emerging clinical potential of cardiovascular gene therapy.
The emerging clinical potential of cardiovascular gene therapy.
复制标题
心血管基因治疗的新兴临床潜力。
DOI：
10.1053/siic.1999.0095
复制
发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Willerson,JT
中科院分区：
文献类型：
--
作者：
Zoldhelyi,P;Eichstaedt,H;Jax,T;McNatt,JM;Chen,ZQ;Shelat,HS;Rose,H;Willerson,JT
尽管取得了相当大的进展，但药物治疗尚未为常见的心血管问题提供完整的解决方案，包括复发性血栓形成、再狭窄和静脉移植物恶化。最佳的药物剂量，重现在建立原理验证的动物研究中达到的血浆浓度，通常毒性太大而无法给药，特别是在长时间给药时。局部基因治疗旨在过表达以下蛋白质：（1）调节VSMC的细胞周期;（2）抑制VSMC迁移;（3）赋予内皮血管保护特性;（4）刺激内皮生长和血管生成。或者，一些方法倾向于抑制被认为促进VSMC增殖和迁移的蛋白质的基因表达。与药物治疗形成鲜明对比的是，局部基因治疗将有益因子的表达限制在受损的血管部位，并且在那里，它可以将该因子的存在延长至数周，并且对于某些基因载体，可以延长至数月。这种方法的临床潜力已经导致了目前评估基因治疗方法对外周和心肌缺血的衰减以及静脉移植物疾病的预防的试验的开始。
Despite considerable progress, pharmacological therapies have not provided a complete solution for common cardiovascular problems, including recurrent thrombosis, restenosis, and vein graft deterioration. Optimal drug dosage, reproducing plasma concentrations achieved in animal studies establishing proof-of-principle, would often be too toxic to administer, especially when given over prolonged periods of time. Local gene therapy aims at overexpressing proteins that:(1) regulate the cell cycle of VSMC;(2) inhibit VSMC migration;(3) endow the endothelium with its vasoprotective properties; and (4) stimulate growth of endothelium and angiogenesis. Alternatively, some approaches tend to suppress gene expression of proteins believed to promote VSMC proliferation and migration. In sharp contrast to drug treatments, local gene therapy limits expression of the beneficial agent to the injured vascular site, and there, it can extend the presence of this agent to weeks and, with some gene vectors, to many months. The clinical potential of this approach has led to the initiation of trials that currently evaluate gene therapy approaches to the attenuation of peripheral and myocardial ischaemia and the prevention of vein graft disease.