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As a metalloendopeptidase, meprin\u2010\u03b1 (Mep1A) critically modulates the activity of proteins and inflammatory cytokines in various diseases. Here, we sought to investigate the functional role of Mep1A in AAA formation and rupture.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>AAA tissues were detected by using real\u2010time PCR (RT\u2010PCR), western blotting (WB), and immunohistochemistry. Further mechanistic studies used RT\u2010PCR, WB, and enzyme\u2010linked immunosorbent assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Mep1A mediated AAA formation by regulating the mast cell (MC) secretion of TNF\u2010\u03b1, which promoted matrix metalloproteinase (MMP) expression and apoptosis in smooth muscle cells (SMCs). Importantly, increased Mep1A expression was found in human AAA tissues and in angiotensin II\u2010induced mouse AAA tissues. Mep1A deficiency reduced AAA formation and increased the survival rate of AAA mice. Pathological analysis showed that Mep1A deletion decreased elastic lamina degradation and SMC apoptosis in AAA tissues. Furthermore, Mep1A was expressed mainly in MCs, wherein it mediated TNF\u2010\u03b1 expression. Mep1A inhibitor actinonin significantly inhibited TNF\u2010\u03b1 secretion in MCs. TNF\u2010\u03b1 secreted by MCs enhanced MMP2 expression in SMCs and promoted SMC apoptosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Taken together, these data suggest that Mep1A may be vital in AAA pathophysiology by regulating TNF\u2010\u03b1 production by MCs. Knocking out Mep1A significantly decreased AAA diameter and improved AAA stability in mice. Therefore, Mep1A is a potential new therapeutic target in the development of AAA.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15019","type":"journal-article","created":{"date-parts":[[2020,2,19]],"date-time":"2020-02-19T05:41:06Z","timestamp":1582090866000},"page":"2872-2885","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Meprin\u2010\u03b1 (Mep1A) enhances TNF\u2010\u03b1 secretion by mast cells and aggravates abdominal aortic aneurysms"],"prefix":"10.1111","volume":"177","author":[{"given":"Ran","family":"Gao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Pathophysiology Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duan","family":"Liu","sequence":"additional","affiliation":[{"name":"Peking Union Medical College 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