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血管紧张素 II 型 1 型受体在腹主动脉瘤中的致病和治疗意义。

Pathogenic and Therapeutic Significance of Angiotensin II Type I Receptor in Abdominal Aortic Aneurysms.

机构信息

Division of Vascular Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, California, CA 94305, United States.

Department of Cardiovascular Medicine and Hypertension, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-0075, Japan.

出版信息

Curr Drug Targets. 2018;19(11):1318-1326. doi: 10.2174/1389450119666180122155642.

Abstract

BACKGROUND

Abdominal aortic aneurysm (AAA) is a chronic degenerative inflammatory disease. Multi-factors including genetic, environmental and lifestyle factors determine the onsets and progression of AAAs. Currently surgical repair remains the only effective aneurysm treatment, but no pharmacological therapy is available for limiting further enlargement of small AAAs and fetal rupture.

OBJECTIVE

This article is to review our current understanding of angiotensin II (Ang II) and its type 1 receptor (AT1) in AAA pathogenesis as well as the translational potential of AT1 receptor blocker (ARB) treatment for treating clinical AAA disease.

RESULTS

While many pathways or molecules have been shown to associate with AAA formation and progression, accumulating evidence indicates the most significant importance of peptide hormone Ang II and its receptor AT1 in AAA pathogenesis and suggests the translational value of targeting inhibition of AT1 in treating clinical AAA disease. This review summarized the influences of AT1 deficiency and pharmacological ARB treatment on experimental AAAs. A discussion has also been made on whether and how ARB medication in AAA patients changes the natural course of clinical AAAs, including aneurysm enlargement rate, rupture and AAA-specific mortality. Additionally, we provided information on two registered clinical trials which are to test the efficacy of telmisartan and valsartan in limiting small AAA enlargement.

CONCLUSION

Ang II/AT1 pathway plays a critical role in aneurysmal pathogenesis. Targeting AT1 via ARB will help establishing novel pharmacological therapies for limiting continuous enlargement of small AAAs in patients.

摘要

背景

腹主动脉瘤(AAA)是一种慢性退行性炎症性疾病。多种因素,包括遗传、环境和生活方式因素,决定了 AAAs 的发作和进展。目前,手术修复仍然是唯一有效的动脉瘤治疗方法,但没有药物治疗可用于限制小型 AAA 的进一步扩大和胎儿破裂。

目的

本文综述了我们目前对血管紧张素 II(Ang II)及其受体 1(AT1)在 AAA 发病机制中的认识,以及 AT1 受体阻滞剂(ARB)治疗用于治疗临床 AAA 疾病的转化潜力。

结果

虽然已经有许多途径或分子与 AAA 的形成和进展有关,但越来越多的证据表明,肽激素 Ang II 和其受体 AT1 在 AAA 的发病机制中具有最重要的意义,并提示靶向抑制 AT1 在治疗临床 AAA 疾病中的转化价值。本综述总结了 AT1 缺乏和药理学 ARB 治疗对实验性 AAA 的影响。还讨论了 ARB 药物治疗在 AAA 患者中是否以及如何改变临床 AAA 的自然病程,包括动脉瘤扩大率、破裂和 AAA 特异性死亡率。此外,我们还提供了两项注册临床试验的信息,这些试验旨在测试替米沙坦和缬沙坦在限制小型 AAA 扩大方面的疗效。

结论

Ang II/AT1 通路在动脉瘤发病机制中起关键作用。通过 ARB 靶向 AT1 将有助于建立新的药理学治疗方法,限制患者小型 AAA 的持续扩大。

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