A comprehensive analysis of differentially expressed genes and pathways in abdominal aortic aneurysm

Abstract

Abstract. The current study aimed to investigate the molecular mechanism underlying abdominal aortic aneurysm (AAA) via various bioinformatics techniques. Gene expression profiling analysis of differentially expressed genes (DEGs) between AAA samples and normal controls was conducted. The Database for Annotation, Visualization and Integrated Discovery tool was utilized to perform Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses for DEGs and clusters from the protein-protein interaction (PPI) network, which was constructed using the Search Tool for the Retrieval of Interacting Genes. In addition, important transcription factors (TFs) that regulated DEGs were investigated. A total of 346 DEGs were identified between AAA samples and healthy controls. Additionally, four clusters were identified from the PPI network. Cluster 1 was associated with sensory perception of smell and the olfactory transduction subpathway. The most significant GO function terms for cluster 2 and 3 were response to virus and defense response, respectively. Cluster 4 was associated with mitochondria-associated functions and the oxidative phosphorylation subpathway. Early growth response-1 (EGR-1), Myc, activating transcription factor 5 (ATF5) and specificity protein (SP) 1:SP3 were identified to be critical TFs in this disease. The present study suggested that the olfactory transduction subpathway, mitochondria and oxidative phosphorylation pathways were involved in AAA, and TFs, such as EGR-1, Myc, ATF5 and SP1:SP3, may be potential candidate molecular targets for this disease.

Aberrant Mitochondrial Dynamics: An Emerging Pathogenic Driver of Abdominal Aortic Aneurysm

“…The current application of genome analysis may provide several new insights into the area. According to the gene expression profiling analysis of differentially expressed genes (DEGs) between AAA samples and normal controls, a total of 436 DEGs were identified using Gene Ontology (GO) and KEGG analyses [42], and four different clusters were identified from the protein-protein interaction network [42]. In addition to the known and traditional pathways involved in the response to viral infection and the defense response indicative of the role of inflammation during AAA, one of the four clusters was associated with mitochondria-associated functions and the oxidative phosphorylation subpathway [42]; a potential role of mitochondrial function in the pathogenesis of AAA was thus proposed.…”

Mitochondrial function in thoracic aortic aneurysms

“…Mitochondrial dysfunction has been associated with arterial aneurysm formation, but most studies have analysed abdominal aortic aneurysms (AAAs) rather than genetic thoracic aneurysmal aorta syndromes. For example, AAAs show differential expression of a number of genes associated with mitochondrial function and oxidative phosphorylation 4 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) gene expression is decreased in human AAA and angiotensin (Ang) II-induced AAA in mice. Similarly, the intima/media layer of AAA vessels showed reduced expression of a number of markers of mitochondrial biogenesis, including PGC1α, ATP synthase, and citrate synthase.…”

Early growth response factor‑1 DNA enzyme 1 inhibits the formation of abdominal aortic aneurysm in rats

“…Egr-1 also regulates the expression of genes related to the development of vascular diseases ( 14 ). Bioinformatics analysis showed that Egr-1 is a key transcription factor in the formation and pathogenesis of AAA ( 15 ). Egr-1 was found to be involved in thrombus formation and the inflammatory pathogenesis of AAA.…”