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[心血管基因治疗的可能性]

[Possibilities for cardiovascular gene therapy].

作者信息

Szelid Zsolt László, Pokreisz Peter, Janssens Stefan, Polák Gyula

机构信息

Gottsegen Györgyi Országos Kardiológiai Intézet, Budapest.

出版信息

Orv Hetil. 2005 May 29;146(22):1189-96.

Abstract

Despite recent advances in the management of cardiovascular disease, atherosclerotic coronary artery disease has remained a prevalent cause of mortality and morbidity among industrialized nations. Although very effective in retarding the progression of ischemic heart disease, pharmacotherapies fail to provide long-term cardio-protection and to effectively recruit contractile function of the damaged left ventricle. Moreover, in many patients the lack of compliance to the daily drug administration further reduces the potential benefit of these strategies. The recent advent of gene-based approaches, however, may represent a potential alternative to target ischemic cardiovascular diseases. During the last decade, gene transfer protocols have shown significant improvement in experimental and clinical applications, including vascular restenosis, chronic peripheral arterial insufficiency, chronic myocardial ischemia, myocardial ischemia-reperfusion injury, and congestive heart failure. Gene-based therapy using potentially beneficial gene sequences represents a promising strategy for site-specific cardiovascular treatment. Transduction of host cells may lead to prolonged bioavailability of the transgene product and may overcome the need for continuous or repetitive drug administrations. Although potential benefits are obvious, they need to be carefully balanced against untoward (inflammatory) side effects. In this review, we discuss the significance of this novel therapeutic strategy, the lessons we have learned from animal studies and how we can envision future use of gene-based strategies in clinical practice.

摘要

尽管近年来心血管疾病的管理取得了进展,但在工业化国家中,动脉粥样硬化性冠状动脉疾病仍然是导致死亡和发病的常见原因。虽然药物治疗在延缓缺血性心脏病进展方面非常有效,但无法提供长期的心脏保护,也不能有效恢复受损左心室的收缩功能。此外,在许多患者中,不遵守每日药物服用规定进一步降低了这些治疗策略的潜在益处。然而,最近基于基因的治疗方法可能是治疗缺血性心血管疾病的一种潜在替代方案。在过去十年中,基因转移方案在实验和临床应用中取得了显著进展,包括血管再狭窄、慢性外周动脉供血不足、慢性心肌缺血、心肌缺血再灌注损伤和充血性心力衰竭。使用潜在有益基因序列的基因治疗是一种有前景的针对特定部位心血管疾病的治疗策略。宿主细胞的转导可能导致转基因产物的生物利用度延长,并可能克服持续或重复给药的需求。虽然潜在益处显而易见,但需要仔细权衡其与不良(炎症)副作用之间的关系。在本综述中,我们讨论了这种新型治疗策略的意义、我们从动物研究中学到的经验教训,以及我们如何设想基于基因的策略在临床实践中的未来应用。

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