Non-coding RNA Contribution to Thoracic and Abdominal Aortic Aneurysm Disease Development and Progression

Abstract

Multiple research groups have started to uncover the complex genetic and epigenetic machinery necessary to maintain cardiovascular homeostasis. In particular, the key contribution of non-coding RNAs (ncRNAs) in regulating gene expression has recently received great attention. Aneurysms in varying locations of the aorta are defined as permanent dilations, predisposing to the fatal consequence of rupture. The characteristic pathology of an aneurysm is characterized by progressive vessel wall dilation, promoted by dying vascular smooth muscle cells and limited proliferation, as well as impaired synthesis and degradation of extracellular matrix components, which at least partially is the result of transmural inflammation and its disruptive effect on vessel wall homeostasis. Currently no conservative pharmacological approach exists that could slow down aneurysm progression and protect from the risk of acute rupture. In the recent past, several non-coding RNAs (mainly microRNAs) have been discovered as being involved in aneurysm progression throughout varying locations of the aorta. Exploring ncRNAs as key regulators and potential therapeutic targets by using antisense oligonucleotide strategies could open up promising opportunities for patients in the near future. Purpose of this current review is to summarize current findings and novel concepts of perspectivly utilizing ncRNAs for future therapeutic and biomarker applications.

Long noncoding RNAs in key cellular processes involved in aortic aneurysms

“…A true aneurysm is defined as a permanent dilatation of the vessel wall, involving all layers. Enlargement > 1.5 times the expected diameter is considered an aneurysm [1]. Close to 90% of aortic aneurysms (AAs) are found in the abdominal aorta, where the typical clinical diameter threshold for an aneurysm is 30 mm, although individual anatomy may vary, and women can have smaller baseline diameters [2].…”

“…MiRNAs have been extensively studied over the past 15 years. Their roles in regulating fundamental mechanisms of vascular disease development in general, and AA in particular, have suggested them as both promising therapeutic targets, and measurable biomarkers of disease progression [1,15,16]. Several miRNA-based clinical trials have been initiated [17,18].…”

Involvement of Myeloid Cells and Noncoding RNA in Abdominal Aortic Aneurysm Disease

“…Furthermore, various miRNAs have been established to be involved in the cell fates of vascular SMCs and in AAA ( Table 2) (60,68,74). However, the evidence on miRNA species involvement in the inflammatory processes driving AAA disease is limited.…”

Molecular Pharmacological Approaches for Treating Abdominal Aortic Aneurysm

“…34) Several clinical studies have demonstrated the altered miRNA expression in both human AAA wall and serum samples. 28,[35][36][37][38][39] Regulation of these miRNA via antagomirs or miRNA-mimics induces a potent therapeutic effect on experimental AAA formation. Silencing the expression of miRNA-29b, -155, -181b, and -712 using antagomirs inhibited elastase or Ang II-induced AAA expansion in a mouse model.…”