Differentially expressed genes and canonical pathways in the ascending thoracic aortic aneurysm – The Tampere Vascular Study

Abstract

Ascending thoracic aortic aneurysm (ATAA) is a multifactorial disease with a strong inflammatory component. Surgery is often required to prevent aortic rupture and dissection. We performed gene expression analysis (Illumina HumanHT-12 version 3 Expression BeadChip) for 32 samples from ATAA (26 without/6 with dissection), and 28 left internal thoracic arteries (controls) collected in Tampere Vascular study. We compared expression profiles and conducted pathway analysis using Ingenuity Pathway Analysis (IPA) to reveal differences between ATAA and a healthy artery wall. Almost 5000 genes were differentially expressed in ATAA samples compared to controls. The most downregulated gene was homeobox (HOX) A5 (fold change, FC = −25.3) and upregulated cadherin-2 (FC = 12.6). Several other HOX genes were also found downregulated (FCs between -25.3 and -1.5, FDR < 0.05). 43, mostly inflammatory, canonical pathways in ATAA were found to be significantly (p < 0.05, FDR < 0.05) differentially expressed. The results remained essentially the same when the 6 dissected ATAA samples were excluded from the analysis. We show for the first time on genome level that ATAA is an inflammatory process, revealing a more detailed molecular pathway level pathogenesis. We propose HOX genes as potentially important players in maintaining aortic integrity, altered expression of which might be important in the pathobiology of ATAA.

Correlation of computed tomography with carotid plaque transcriptomes associates calcification with lesion-stabilization

“…We and others [16,17] recently confirmed that molecular pathways related to calcification dominate in end-stage carotid plaques. While osteolytic processes, suggesting reduced calcification, were prevalent in plaques from symptomatic patients, plaques from patients on statin therapy and asymptomatic ones were enriched in processes associated with increased calcification [8].…”

Low-dose ionizing radiation exposure represses the cell cycle and protein synthesis pathways in in vitro human primary keratinocytes and U937 cell lines

“…For IPA analyses, we used two scores: an ‘enrichment’ score (Fisher’s exact test P -value) that measures the overlap of observed and predicted regulated gene sets, and a Z-score that assesses the match of observed and predicted upregulation/downregulation patterns [ 21 ]. The inclusion criteria for genes selected for the analysis was a fold change > ± .8 [ 22 ].…”

Mapping Semaphorins and Netrins in the Pathogenesis of Human Thoracic Aortic Aneurysms

“…Interestingly, pathway analysis uncovered novel axonal guidance genes that were distinctly elevated in TAA. In a recently published study, this pathway was also detected in a larger cohort of patients suffering from TAA although the authors did not focus their analysis on these axonal cues [19]. Notably, two of the most essential families of genes in the axon guidance pathway, Netrins and Semaphorins were increased in TAA aortic tissue suggesting they could have a causative role in the degenerative mechanisms in TAA development.…”

“…For RNA Sequencing analysis, we used histologically non-diseased and non-atherosclerotic ITAs as controls because due to logistic reasons we did not yet have access to non-diseased cadaver aortic tissues. ITAs share similar features with aorta and have also been used in previous studies as control samples for ascending and descending TAA [19,48]. Notably, both ITA and TAA samples were processed and analyzed within same experimental settings to avoid methodological artefacts.…”