Role of Noncoding RNAs in the Pathogenesis of Abdominal Aortic Aneurysm Possible Therapeutic Targets?

• Type of Material: Article
• Authors: Sandeep Kumar, Emory University; Reinier A. Boon, Goethe University; Lars Maegdefessel, Technical University Munich; Stefanie Dimmeler, Goethe University; Hanjoong Jo, Emory University
• Language: English
• Date: 2019-02-15
• Publisher: Lippincott Williams & Sons
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 American Heart Association, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1161/CIRCRESAHA.118.312438
• Title of Journal or Parent Work: Circulation Research
• Volume: 124
• Issue: 4
• Start Page: 619
• End Page: 630
• Grant/Funding Information: RAB is funded by the German Research Foundation (DFG, SFB834), the European Research Council (ERC, NOVA), the German Center for Cardiovascular Research (DZHK), the Amsterdam Academic Alliance (AAA), and the Netherlands Organisation for Scientific Research (NWO, Vidi).; LM is funded through the European Research Council (ERC NORVAS), the German Center for Cardiovascular Research (DZHK), the German Research Foundation (DFG, Heisenberg Programm), the Swedish Research Council (VR), and the Swedish Heart-Lung-Foundation (HLF).; SD is funded through the Excellence Cluster Cardiopulmonary Systems (German Research Foundation) and the LOEWE (Landes-Offensive zur Entwicklung Wissenschaftlich-ökonomischer Exzellenz) Centre for Cell and Gene Therapy (State of Hesse) and the German Research Foundation (SFB834).; This work was supported by funding from National Institutes of Health grants HL119798 and HL095070 to HJ.
• Keywords: Delivery; Reveals; Microronas; microRNAs; dissection; biomarkers; long noncoding RNA; Science & Technology; Peripheral Vascular Disease; Apoptosis; Endothelial cells; Cardiovascular System & Cardiology; aortic aneurysms; Smooth muscle cells; Gene expression; Exosomes; Angiotensin-II; Hematology; Cardiac & Cardiovascular Systems; Mesenchymal stem cells; Life Sciences & Biomedicine
• Research Categories: Engineering, Biomedical; Biology, Physiology; Biology, Cell

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.