Bioinformatics Analysis Reveals Cell Cycle-Related Gene Upregulation in Ascending Aortic Tissues From Murine Models

Abstract

Thoracic aortic aneurysm and dissection (TAAD) is a high-risk aortic disease. Mouse models are usually used to explore the pathological progression of TAAD. In our studies, we performed bioinformatics analysis on a microarray dataset (GSE36778) and verified experiments to define the integrated hub genes of TAAD in three different mouse models. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein–protein interaction (PPI) network analyses, and histological and quantitative reverse transcription-PCR (qRT–PCR) experiments were used in our study. First, differentially expressed genes (DEGs) were identified, and twelve common differentially expressed genes were found. Second, genes related to the cell cycle and inflammation were enriched by using GO and PPI. We focused on filtering and validating eighteen hub genes that were upregulated. Then, expression data from human ascending aortic tissues in the GSE153434 dataset were also used to verify our findings. These results indicated that cell cycle-related genes participate in the pathological mechanism of TAAD and provide new insight into the molecular mechanisms of TAAD.

The Effect of N6-Methyladenosine Regulators and m6A Reader YTHDC1-Mediated N6-Methyladenosine Modification Is Involved in Oxidative Stress in Human Aortic Dissection

“…GO-BP results showed that these genes were extensively involved in cell cycle-related processes, as well as Wnt signaling pathway and planar cell polarity pathway. A bioinformatics study found that cell cycle-related genes were significantly upregulated in thoracic aortic aneurysm and dissection tissues in a mouse model, and they were essential for cell proliferation [40]. In response to changes in the local vascular environment, vascular smooth muscle cells proliferate to alter the differentiation/contraction phenotype [41].…”

S100A4 Is a Key Facilitator of Thoracic Aortic Dissection

“…In addition, recent studies have shown that extracellular S100A4 can induce tumor cells to produce pro-inflammatory cytokines [16,17] and converts VSMCs to a pro-inflammatory phenotype, which contributes to the formation and rupture of atherosclerotic plaques [18]. The differential expression of S100A4 has been reported in both TAD [19] and abdominal aortic aneurysm [20]. Moreover, S100A4 expression is up-regulated in TAD [21].…”

Applying multi-omics techniques to the discovery of biomarkers for acute aortic dissection

“…The risk of acute aortic events is complicated by a range of genetic variants affecting the development and remodeling of the thoracic aortic wall ( 88 ), and we also prefer to consider these pathogenic variants as genetic triggers of AAD. The likelihood of these genes being mutated to cause AAD increases when they are involved in the cell cycle ( 89 ), collagen metabolism ( 90 ), extracellular matrix maintenance ( 91 , 92 ), vascular remodeling, smooth muscle cell proliferation, and the onset of hypertension ( 93 ). The occurrence of all these rare variants will need to be verified in the future by testing large samples and improving the precision of our technology.…”