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To investigate the underlying mechanisms of AAA initiation and progression, seven AAA datasets related to human and mice were downloaded from the GEO database and reanalysed in the present study. After comprehensive bioinformatics analysis, we identified the enriched pathways associated with inflammation responses, vascular smooth muscle cell (VSMC) phenotype switching and cytokine secretion in AAA. Most importantly, we identified ATPase Na<jats:sup>+<\/jats:sup>\/K<jats:sup>+<\/jats:sup> transporting subunit alpha 2 (ATP1A2) as a key gene that was significantly decreased in AAA samples of both human and mice; meanwhile, its reduction mainly occurred in VSMCs of the aorta; this finding was validated by immunostaining and Western blot in human and mouse AAA samples. Furthermore, we explored the potential upstream transcription factors (TFs) that regulate ATP1A2 expression. We found that the TF AT\u2010rich interaction domain 3A (ARID3A) bound the promoter of ATP1A2 to suppress its expression. Our present study identified the ARID3A\u2010ATP1A2 axis as a novel pathway in the pathological processes of AAA, further elucidating the molecular mechanism of AAA and providing potential therapeutic targets for AAA.<\/jats:p>","DOI":"10.1111\/jcmm.17301","type":"journal-article","created":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T06:41:36Z","timestamp":1650436896000},"page":"2866-2880","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Comprehensive analysis identified a reduction in ATP1A2 mediated by ARID3A in abdominal aortic aneurysm"],"prefix":"10.1111","volume":"26","author":[{"given":"Qunhui","family":"Wang","sequence":"first","affiliation":[{"name":"Division of Cardiothoracic and Vascular Surgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan Hubei 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