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精细化管理腹主动脉瘤。

Micromanaging abdominal aortic aneurysms.

机构信息

Department of Medicine, Karolinska Institute, Stockholm SE-17176, Sweden.

出版信息

Int J Mol Sci. 2013 Jul 11;14(7):14374-94. doi: 10.3390/ijms140714374.

Abstract

The contribution of abdominal aortic aneurysm (AAA) disease to human morbidity and mortality has increased in the aging, industrialized world. In response, extraordinary efforts have been launched to determine the molecular and pathophysiological characteristics of the diseased aorta. This work aims to develop novel diagnostic and therapeutic strategies to limit AAA expansion and, ultimately, rupture. Contributions from multiple research groups have uncovered a complex transcriptional and post-transcriptional regulatory milieu, which is believed to be essential for maintaining aortic vascular homeostasis. Recently, novel small noncoding RNAs, called microRNAs, have been identified as important transcriptional and post-transcriptional inhibitors of gene expression. MicroRNAs are thought to "fine tune" the translational output of their target messenger RNAs (mRNAs) by promoting mRNA degradation or inhibiting translation. With the discovery that microRNAs act as powerful regulators in the context of a wide variety of diseases, it is only logical that microRNAs be thoroughly explored as potential therapeutic entities. This current review summarizes interesting findings regarding the intriguing roles and benefits of microRNA expression modulation during AAA initiation and propagation. These studies utilize disease-relevant murine models, as well as human tissue from patients undergoing surgical aortic aneurysm repair. Furthermore, we critically examine future therapeutic strategies with regard to their clinical and translational feasibility.

摘要

在老龄化和工业化的世界中,腹主动脉瘤(AAA)疾病对人类发病率和死亡率的影响日益增加。因此,人们已经做出了非凡的努力,来确定患病主动脉的分子和病理生理学特征。这项工作旨在开发新的诊断和治疗策略,以限制 AAA 的扩张,并最终防止破裂。来自多个研究小组的贡献揭示了一个复杂的转录和转录后调控环境,这被认为对于维持主动脉血管的稳态至关重要。最近,新型的小非编码 RNA,称为 microRNAs,被确定为重要的转录和转录后基因表达抑制剂。microRNAs 被认为通过促进 mRNA 降解或抑制翻译来“微调”其靶信使 RNA(mRNA)的翻译输出。随着人们发现 microRNAs 在多种疾病中起到强大的调控作用,microRNAs 作为潜在的治疗实体被深入研究是合乎逻辑的。本综述总结了关于在 AAA 发生和发展过程中 microRNA 表达调节的有趣发现,这些发现涉及到与疾病相关的小鼠模型,以及接受手术主动脉瘤修复的患者的人类组织。此外,我们还批判性地评估了未来治疗策略的临床和转化可行性。

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