MicroRNAs as potential biomarkers in aortic diseases

Aims: MicroRNAs (miRNAs) are promising as potential biomarkers because their expression pattern is reflective of underlying pathophysiologic processes. Recent studies reported on altered miRNAs in bicuspid aortic valve and described how alterations in microRNA levels may result in aortic valve calcification. However, the putative roles of these miRNAs in aortic diseases are unexplained.

Methods: In order to identify miRNAs potentially modulated in aortic diseases, PIQOR^TM miRXplore Microarrays containing 1421 miRNAs were used for pooled tissues of each three patients with acute aortic dissection (AAD), thoracic aortic aneurysm (TAA), and Marfan syndrome (MS). Then in a collective of 15 patients with AAD (mean age 56.9±16.9 years), 7 patients with bicuspid TAA (mean age 60.2±14.5 years), and a 49 years MS, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to validate the miRNA array results. We also performed in silico analysis to predict target genes.

Results: 25 miRNAs were screend to be differenzially expressed in AAD compared with TAA. MiR-21, let-7g, miR-145 are upregulated with 52%, 83%, and 69% respectively. MiR-214 and miR-125A-5p were downregulated and the validation of miR-214 in qRT-PCR showed a distinguishable decreased level in AAD compared to TAA. Analysis to identify the targets of miR-145 revealed that the 3′UTR of the transforming growth factor beta gene, known in MS, harbors putative binding sites for it.

Discussion: Our preliminary data suggest that let-7g, miR-145, and miR-214 are promising as candidate biomarkers in AAD and that miR-21 and miR-125A-5p are specific to various aortic disease states.