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

We hypothesized that aquaporins (AQPs), membrane proteins facilitating water and small molecule translocation, are implicated in thoracic aortic aneurysm (TAA) pathogenesis through their deregulation, impairing water transport and detoxification.

Raw data were extracted from a publicly available data set. Gene expression profiling was performed with mRNA/microRNA (miRNA) microarrays and differentially expressed genes (DEGs) were identified. Biopsy specimens for RNA and histologic analyses were obtained from dilated (>45 mm) and nondilated (<40 mm) aortas. Aortic specimens with diameter between 40 and 45 mm were excluded. Significant correlations between 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.

A total of 86 samples were included (43 TAAs and 43 normal control samples) in the study. Data were available for 11 of 13 (85%) AQPs. Four DEGs were identified (AQP2, AQP5, AQP10, AQP11). All DEGs were significantly downregulated in TAA (P < .005). Significant positive correlations were demonstrated between AQP2 and AQP5, AQP2 and AQP10, and AQP5 and AQP10. All 4 DEGs were associated with fair discrimination and calibration traits. The interactome of the DEGs demonstrated 20 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 microtubule severing. The top 5 related miRNA families were also identified.

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