Unbiased Profile of MicroRNA Expression in Ascending Aortic Aneurysm Tissue Appoints Molecular Pathways Contributing to the Pathology

Background: Complex etiopathogenesis of ascending aortic aneurysm suggests contribution of epigenetic mechanisms in its development. Several studies appointed microRNAs (miRs) as essential epigenetic factors in various human diseases; however, little is known about their role in ascending aortic aneurysm. Therefore, the aim of this study was to perform unbiased molecular screening of miRs expression in aneurysmal tissue and establish their functions on a transcriptional level.

Methods: Samples of ascending aortic tissue were obtained from 15 patients, and total RNA was isolated separately from aneurysmal and unaffected aortic tissue obtained from the same patient. Expression of the complete panel of human miRs was assessed by quantitative real-time polymerase chain reaction. Using bioinformatic tools, 13 genes were selected that were putatively regulated by overexpressed miRs. Expression level of transcripts were evaluated by quantitative real-time polymerase chain reaction and correlated with their targeting miRs.

Results: Overexpression of 10 miRs distinguished aneurysmal tissue from the unchanged one. These miRs were involved in cell senescence (miR-191-5p), maintenance of vascular integrity (miR-126-3p and miR-374-5p), nitric oxide-dependent vascular relaxation (miR-21-5p), smooth muscle differentiation, and contractility (miR-145- 3p, miR-29c-3p, miR-133a-3p, miR-186-5p, miR-143-3p, and miR-24-3p), and correlated with abundance of its miR targets.

Conclusions: Altered expression of particular miRs selectively in the affected tissue indicate their role as factors that trigger pathways of aneurysmal transformation. Limited reparative properties due to overexpression of miR-191 may play a crucial role for aneurysm enlargement, whereas nitric oxide-dependent relaxation of vascular smooth muscle mediated by miR-21 offers an attractive explanation of the aneurysm's initiation, and is confirmed in experimental conditions.