Open AccessComprehensive analysis identified a reduction in ATP1A2 mediated by ARID3A in abdominal aortic aneurysm
Author(s) -
Wang Qunhui,
Li Na,
Guo Xian,
Huo Bo,
Li Rui,
Feng Xin,
Fang Zemin,
Zhu XueHai,
Wang Yixiang,
Yi Xin,
Wei Xiang,
Jiang DingSheng
Publication year - 2022
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17301
Subject(s) - abdominal aortic aneurysm , western blot , immunostaining , aorta , vascular smooth muscle , cancer research , medicine , pathology , biology , aneurysm , gene , immunohistochemistry , biochemistry , surgery , smooth muscle
Abstract Abdominal aortic aneurysm (AAA) is characterized by abdominal aorta dilatation and progressive structural impairment and is usually an asymptomatic and potentially lethal disease with a risk of rupture. 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 + /K + 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‐rich interaction domain 3A (ARID3A) bound the promoter of ATP1A2 to suppress its expression. Our present study identified the ARID3A‐ATP1A2 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.