[New antithrombotic therapy approaches in coronary heart disease--prospects for gene therapy].
[New antithrombotic therapy approaches in coronary heart disease--prospects for gene therapy].
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冠心病抗血栓治疗新途径——基因治疗的前景[J].
DOI：
10.1007/s003920070134
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Zoldhelyi,P
中科院分区：
文献类型：
--
作者：
Jax,TW;Eichstaedt,HC;Shelat,HS;Barnhart,MK;Lichtenberg,MW;Willerson,JT;Zoldhelyi,P
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。局部基因治疗的目的是过表达调节血管平滑肌细胞细胞周期、抑制血管平滑肌细胞迁移、增强血管内皮保护作用的蛋白质。或者，一些方法倾向于抑制被认为促进血管平滑肌细胞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损伤的血管部位，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。这篇综述总结和讨论了抗血栓基因治疗方法，用于预防再狭窄和晚期血栓形成后，基于导管的血运重建。
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. Local gene therapy aims at overexpressing proteins that regulate the cell cycle of vascular smooth muscle cells, inhibit vascular smooth muscle cell migration, endow the endothelium with enhanced vasoprotective properties. Alternatively, some approaches tend to suppress gene expression of proteins believed to promote vascular smooth muscle cell proliferation and migration. In sharp contrast to drug treatments, local gene therapy limits expression of the beneficial agent to the injured vascular site, where it can extend the presence of this agent to weeks and, with some gene vectors, to many months. This review summarizes and discusses antithrombotic gene therapy approaches for the prevention of restenosis and late thrombosis after catheter-based revascularizations.