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腹主动脉瘤的药物治疗

Pharmacotherapy of abdominal aortic aneurysms.

作者信息

Dawson Joe, Choke Edward, Sayed Saiqa, Cockerill Gillian, Loftus Ian, Thompson Matt M

机构信息

Department of Vascular Surgery, St. George's, University of London, St. George's Hospital, UK.

出版信息

Curr Vasc Pharmacol. 2006 Apr;4(2):129-49. doi: 10.2174/157016106776359817.

DOI:10.2174/157016106776359817
PMID:16611155
Abstract

Aortic aneurysms account for 10,000 deaths annually in the UK, due to rupture. At present the only effective therapeutic strategy to treat abdominal aortic aneurysms is to surgically repair them; this carries an elective mortality of up to 10%. Recent advances in vascular biology have led to a greater understanding of the pathophysiological process that causes aortic aneurysms to expand and rupture. Key pathological processes include widespread aortic inflammation, proteolytic degradation of the extracellular matrix, neovascularisation and generation of reactive oxygen species. Identification of these processes has lead to pharmacological strategies to prevent aneurysm expansion and rupture. Many of these strategies have undergone proof of concept in animal models and some have now entered clinical trials. This review outlines current thinking regarding the molecular events leading to aneurysm expansion and explains how these processes may be inhibited. Experimental data on agents retarding aneurysm expansion in animal models are discussed. A significant proportion of the review details pharmacological agents that have undergone or are undergoing clinical trials. Pharmacological treatment for abdominal aneurysms is urgently required given the number of small aneurysms being diagnosed by screening programmes. This is a rapidly evolving field and one in which translation from experimental research to clinical practice is anticipated within 5 years.

摘要

在英国,主动脉瘤每年导致10000人因破裂而死亡。目前,治疗腹主动脉瘤的唯一有效治疗策略是手术修复;这一手术的择期死亡率高达10%。血管生物学的最新进展使人们对导致主动脉瘤扩张和破裂的病理生理过程有了更深入的了解。关键的病理过程包括广泛的主动脉炎症、细胞外基质的蛋白水解降解、新生血管形成和活性氧的产生。对这些过程的认识催生了预防动脉瘤扩张和破裂的药理学策略。其中许多策略已在动物模型中得到概念验证,有些现已进入临床试验阶段。本综述概述了目前关于导致动脉瘤扩张的分子事件的观点,并解释了如何抑制这些过程。讨论了在动物模型中延缓动脉瘤扩张的药物的实验数据。鉴于筛查项目诊断出的小动脉瘤数量众多,腹主动脉瘤的药物治疗迫在眉睫。这是一个快速发展的领域,预计在5年内将实现从实验研究到临床实践的转化。

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