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时光倒流:通过药物治疗使腹主动脉瘤消退

Turning back the clock: regression of abdominal aortic aneurysms via pharmacotherapy.

作者信息

Aoki Hiroki, Yoshimura Koichi, Matsuzaki Masunori

机构信息

Department of Molecular Cardiovascular Biology, Yamaguchi University School of Medicine, 1-1-1 Minami Kogushi, Ube, Yamaguchi, 755-8505, Japan.

出版信息

J Mol Med (Berl). 2007 Oct;85(10):1077-88. doi: 10.1007/s00109-007-0213-2. Epub 2007 May 24.

Abstract

Abdominal aortic aneurysm (AAA) is a common disease that causes progressive expansion and rupture of the aorta with high mortality. There is a large and unmet need for nonsurgical treatment for AAA. Research has shown that an intricate network of inflammatory cells and interstitial cells contributes to the formation of AAA by producing pro-inflammatory mediators that activate enzymes to degrade the extracellular matrix (ECM) and impair ECM biosynthesis. Pharmacological agents such as statins and angiotensin-converting enzyme inhibitors may promote tissue stabilization in AAA by diminishing pro-inflammatory signaling and normalizing metabolism of the ECM. Our recent experiments in animal models demonstrate that inhibition of c-Jun N terminal kinase (JNK) inhibits multiple pathological processes and causes regression of established AAA. Thus, emerging evidence indicates that pharmacological intervention targeting pro-inflammatory signaling and abnormal ECM metabolism is a promising strategy for treatment of AAA.

摘要

腹主动脉瘤(AAA)是一种常见疾病,可导致主动脉进行性扩张和破裂,死亡率很高。对于AAA的非手术治疗存在巨大且未满足的需求。研究表明,炎症细胞和间质细胞的复杂网络通过产生促炎介质来促进AAA的形成,这些促炎介质激活酶以降解细胞外基质(ECM)并损害ECM生物合成。他汀类药物和血管紧张素转换酶抑制剂等药物可能通过减少促炎信号传导和使ECM代谢正常化来促进AAA中的组织稳定。我们最近在动物模型中的实验表明,抑制c-Jun氨基末端激酶(JNK)可抑制多种病理过程并使已形成的AAA消退。因此,新出现的证据表明,针对促炎信号传导和异常ECM代谢的药物干预是治疗AAA的一种有前景的策略。

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