Non coding RNAs in aortic aneurysmal disease

Abstract

An aneurysm is a local dilatation of a vessel wall which is >50% its original diameter. Within the spectrum of cardiovascular diseases, aortic aneurysms are among the most challenging to treat. Most patients present acutely after aneurysm rupture or dissection from a previous asymptomatic condition and are managed by open surgical or endovascular repair. In addition, patients may harbor concurrent disease contraindicating surgical intervention. Collectively, these factors have driven the search for alternative methods of identifying, monitoring and treating aortic aneurisms using less invasive approaches. Non-coding RNA (ncRNAs) are emerging as new fundamental regulators of gene expression. The small microRNAs have opened the field of ncRNAs capturing the attention of basic and clinical scientists for their potential to become new therapeutic targets and clinical biomarkers for aortic aneurysm. More recently, long ncRNAs (lncRNAs) have started to be actively investigated, leading to first exciting reports, which further suggest their important and yet largely unexplored contribution to vascular physiology and disease. This review introduces the different ncRNA types and focus at ncRNA roles in aorta aneurysms. We discuss the potential of therapeutic interventions targeting ncRNAs and we describe the research models allowing for mechanistic studies and clinical translation attempts for controlling aneurysm progression. Furthermore, we discuss the potential role of microRNAs and lncRNAs as clinical biomarkers.

Keywords: aneurysms; biomarkers; long non-coding RNAs; microRNAs; therapeutic targets; vascular cells.

Figure 1

A computed tomography (CT) scan with contrast showing an abdominal aortic aneurysm. This aneurysm was asymptomatic and found during routine surveillance scanning of a 67 year old male. Calcified atherosclerotic plaque is noted on the aneurysm wall and in the distal aorta (a).

Figure 2

Ascending aortic aneurysm. This is an aorta of a 37 year old male who was found to have a 7.7 cm saccular ascending aortic aneurysm associated with a leaking bicuspid aortic valve. The remainder of the aorta is normal caliber. (A) CT reconstruction of the whole aorta with ascending aortic aneurysm (a), with a normal caliber abdominal aorta (b). (B) Surgical view of this aneurysm; (C) Dacron graft after surgical replacement.

Figure 3

Thoracic aorta aneurysms. MRI scans of the ascending aorta in a 17 year old girl with multiple thoracic aortic aneurysms. In (i), it is clearly visible a large saccular aneurysm of the aortic arch just distal to the right carotid artery (RCA) and a second large saccular aneurysm in the descending aorta. In (ii), the MRI scan shows the ascending and descending aorta. The left subclavian artery (LSA) comes off the descending aorta in between two large saccular aneurysms.