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

• Authors: Sandeep Kumar, Emory University; Reinier A. Boon, Goethe University; Lars Maegdefessel, Technical University Munich; Stefanie Dimmeler, Goethe University; Hanjoong Jo, Emory University
• Journal Title: Circulation Research
• Volume: Volume 124, Number 4
• Publisher: Lippincott Williams & Sons | 2019-02-15, Pages 619-630
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1161/CIRCRESAHA.118.312438
• Subjects: Biology, Cell; Engineering, Biomedical; Biology, Physiology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease; Cardiovascular System & Cardiology; aortic aneurysms; biomarkers; dissection; long noncoding RNA; microRNAs; Smooth muscle cells; Mesenchymal stem cells; Angiotensin-II; Gene expression; Endothelial cells; Delivery; Microronas; Apoptosis; Exosomes; Reveals

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.