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.

Highlights

  • Aortic aneurysms (AAs) are asymmetrical dilations of the aorta with diameters >1.5 times the normal size (Kent, 2014)

  • This review focuses on the contribution of non-coding RNAs to AA development and progression, and discusses their potential therapeutic value in this context

  • Overexpression of miR-24 in murine models was able to significantly decrease chitinase 3-like 1′ (Chi3l1) levels, leading to arrested abdominal AAs (AAAs) development and reduced immune responses and cytokine activities, suggesting that miR-24 downregulation contributes to aneurysm growth

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Summary

Introduction

Aortic aneurysms (AAs) are asymmetrical dilations of the aorta with diameters >1.5 times the normal size (Kent, 2014). In the context of AAAs, miR-24-Chi3l1 interactions appear to have broad effects on all cells present in the aortic wall, such as the regulation of macrophage survival and cytokine synthesis, promotion of aortic SMC migration and cytokine production, and stimulation of adhesion molecule expression in vascular ECs. overexpression of miR-24 in murine models was able to significantly decrease Chi3l1 levels, leading to arrested AAA development and reduced immune responses and cytokine activities, suggesting that miR-24 downregulation contributes to aneurysm growth.

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