A Transcriptomic Analysis Exploring the Role of Aquaporins in the Pathogenesis of Thoracic Aortic Aneurysm.

Background: We hypothesized that Aquaporins (AQPs), membrane proteins facilitating water and small molecule translocation, implicate in thoracic aortic aneurysm (TAA) pathogenesis via their deregulation, impairing water transport and detoxification.

Methods: Raw data was extracted from a publicly available dataset. Gene expression profiling was performed with mRNA/miRNA microarrays and differentially expressed genes (DEGs) were identified. Biopsies for RNA and histological analyses were obtained from dilated (>45mm) and non-dilated (<40mm) aortas. Aortic specimens with diameter between 40-45 mm were excluded. Significant correlations among DEGs, along with their discrimination and calibration traits were assessed. Regarding DEGs, functional enrichment analysis uncovered the related interactome, CpG islands, biological functions, and miRNAs.

Results: A total of 86 samples were included (43 TAA and 43 normal control samples) in the present study. There was available data for 11 out of 13 (85%) AQPs. Four DEGs were identified (AQP2, AQP5, AQP10, AQP11). All DEG were significantly downregulated in TAA (p<0.005). Significant positive correlations were demonstrated between AQP2-AQP5, AQP2-AQP10, and AQP5-AQP10. All four DEGs were associated with fair discrimination and calibration traits. The DEGs interactome demonstrated twenty related genes and the CpG islands for each DEG. The primary biological functions related to DEGs were translocation of water and glycerol, along with regulation of hydrogen peroxidase and microtubules severing. The top five related miRNA families were also identified.

Conclusions: This hypothesis-driven analysis uncovered a role of certain AQPs in the TAA pathogenesis. Further research is needed to evaluate their use as possible biomarkers in the diagnosis and treatment of TAA.