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非编码 RNA 在腹主动脉瘤发病机制中的作用。

Role of Noncoding RNAs in the Pathogenesis of Abdominal Aortic Aneurysm.

机构信息

From the Wallace H. Coulter Department of Biomedical Engineering, Emory University, Georgia Institute of Technology, Atlanta (S.K., H.J.).

Institute for Cardiovascular Regeneration, Center of Molecular Medicine, Goethe University, Frankfurt, Germany (R.A.B., S.D.).

出版信息

Circ Res. 2019 Feb 15;124(4):619-630. doi: 10.1161/CIRCRESAHA.118.312438.

Abstract

Abdominal aortic aneurysm (AAA) is a local dilatation of the abdominal aortic vessel wall and is among the most challenging cardiovascular diseases as without urgent surgical intervention, ruptured AAA has a mortality rate of >80%. Most patients present acutely after aneurysm rupture or dissection from a previously asymptomatic condition and are managed by either surgery or endovascular repair. Patients usually are old and have other concurrent diseases and conditions, such as diabetes mellitus, obesity, and hypercholesterolemia making surgical intervention more difficult. Collectively, these issues have driven the search for alternative methods of diagnosing, monitoring, and treating AAA using therapeutics and less invasive approaches. Noncoding RNAs-short noncoding RNAs (microRNAs) and long-noncoding RNAs-are emerging as new fundamental regulators of gene expression. Researchers and clinicians are aiming at targeting these microRNAs and long noncoding RNAs and exploit their potential as clinical biomarkers and new therapeutic targets for AAAs. While the role of miRNAs in AAA is established, studies on long-noncoding RNAs are only beginning to emerge, suggesting their important yet unexplored role in vascular physiology and disease. Here, we review the role of noncoding RNAs and their target genes focusing on their role in AAA. We also discuss the animal models used for mechanistic understanding of AAA. Furthermore, we discuss the potential role of microRNAs and long noncoding RNAs as clinical biomarkers and therapeutics.

摘要

腹主动脉瘤 (AAA) 是腹主动脉壁的局部扩张,是最具挑战性的心血管疾病之一,因为如果不紧急进行外科手术干预,破裂的 AAA 的死亡率超过 80%。大多数患者在动脉瘤破裂或夹层后急性出现,或在先前无症状的情况下出现,通过手术或血管内修复进行治疗。患者通常年龄较大,同时患有其他合并症和疾病,如糖尿病、肥胖症和高胆固醇血症,这使得手术干预更加困难。这些问题共同促使人们寻找使用治疗方法和微创方法诊断、监测和治疗 AAA 的替代方法。非编码 RNA-短非编码 RNA(microRNAs)和长非编码 RNA-正在成为基因表达新的基本调控因子。研究人员和临床医生旨在靶向这些 microRNAs 和长非编码 RNA,并利用它们作为 AAA 的临床生物标志物和新的治疗靶点的潜力。虽然 microRNAs 在 AAA 中的作用已经确立,但关于长非编码 RNA 的研究才刚刚开始出现,表明它们在血管生理学和疾病中的重要但尚未探索的作用。在这里,我们回顾了非编码 RNA 及其靶基因的作用,重点介绍它们在 AAA 中的作用。我们还讨论了用于 AAA 机制理解的动物模型。此外,我们讨论了 microRNAs 和长非编码 RNA 作为临床生物标志物和治疗方法的潜在作用。

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