Abdominal aortic aneurysms (AAA) are a complex disease with an unclear pathomechanism. A positive family history is emphasized as a significant risk factor, and a nonspecific model of inheritance suggests participation of epigenetic regulation in the pathogenesis of this disease. Past studies have implicated microRNAs in the development of AAA; therefore in this project, we measured miR-191 levels in AAA patients and compared them with a control group. We found that miR-191 levels were significantly elevated in aneurysmal patients, although this did not correlate with the available clinical data. We then developed an in vitro model where, using cells with an endothelial phenotype, we determined the effect of miR-191 on the transcriptome using RNA sequencing. Subsequent pathway analysis established that some of the perturbations mediated by miR-191 can be explained by several processes which have long been observed and described in literature as accompanying the development of abdominal aortic aneurysms.

Non-coding RNAs constitute a heterogeneous group of molecules that lack the ability to encode proteins but retain the potential ability to influence cellular processes through a regulatory mechanism. Of these proteins, microRNAs, long non-coding RNAs, and more recently, circular RNAs have been the most extensively described. However, it is not entirely clear how these molecules interact with each other. For circular RNAs, the basics of their biogenesis and properties are also lacking. Therefore, in this study we performed a comprehensive analysis of circular RNAs in relation to endothelial cells. We identified the pool of circular RNAs present in the endothelium and showed their spectrum and expression across the genome. Using different computational strategies, we proposed approaches to search for potentially functional molecules. In addition, using data from an in vitro model that mimics conditions in the endothelium of an aortic aneurysm, we demonstrated altered expression levels of circRNAs mediated by microRNAs.