{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:18:31Z","timestamp":1790713111783,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,10,17]],"date-time":"2018-10-17T00:00:00Z","timestamp":1539734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["91639110"],"award-info":[{"award-number":["91639110"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["91539203"],"award-info":[{"award-number":["91539203"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81730010"],"award-info":[{"award-number":["81730010"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81500326"],"award-info":[{"award-number":["81500326"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81170287"],"award-info":[{"award-number":["81170287"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7172195"],"award-info":[{"award-number":["7172195"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p>\n<jats:p>Thoracic aortic aneurysm and dissection (TAAD) is characterized by extracellular matrix remodelling and an inflammatory response. Evidence suggests that <jats:italic>ADAMTS1<\/jats:italic> is closely associated with TAAD development, but whether it contributes to the pathophysiology of TAAD remains unknown.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p>\n<jats:p>We generated inducible postnatal <jats:italic>ADAMTS1<\/jats:italic> knockout mice and found that <jats:italic>ADAMTS1<\/jats:italic> deficiency attenuated \u03b2\u2010aminopropionitrile\u2010dependent TAAD formation and rupture. Furthermore, <jats:italic>ADAMTS1<\/jats:italic> deficiency suppressed neutrophil and macrophage infiltration by inhibiting inflammatory cytokine levels and macrophage migration during the early stage of \u03b2\u2010aminopropionitrile\u2010induced TAAD. <jats:italic>ADAMTS1<\/jats:italic> could be a new therapeutic target for TAAD.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Thoracic aortic aneurysm and dissection (TAAD), as a life\u2010threatening cardiovascular disease, is characterized by extracellular matrix remodelling and an inflammatory response. A disintegrin and metalloproteinase with thrombospondin motifs 1 (<jats:italic>ADAMTS1<\/jats:italic>) is an inflammation\u2010related protein that is able to degrade extracellular matrix proteins in arteries. Herein, we investigated whether <jats:italic>ADAMTS1<\/jats:italic> contributes to the pathophysiology of TAAD in mice. Using the mouse model of \u03b2\u2010aminopropionitrile (BAPN)\u2010induced TAAD, we found that <jats:italic>ADAMTS1<\/jats:italic> expression was upregulated beginning in the early stage of TAAD development and localized predominantly in the aortic adventitia. <jats:italic>ADAMTS1<\/jats:italic>\u2010floxed mice and whole\u2010body tamoxifen\u2010inducible <jats:italic>ADAMTS1<\/jats:italic> knockout mice (<jats:italic>ADAMTS1<\/jats:italic><jats:sup>flox\/flox<\/jats:sup> Ubc\u2010Cre<jats:sup>ERT2+<\/jats:sup>, <jats:italic>ADAMTS1<\/jats:italic> KO) were generated to investigate the direct causal role of <jats:italic>ADAMTS1<\/jats:italic> in TAAD development. The incidence and rupture rates of BAPN\u2010induced TAAD in <jats:italic>ADAMTS1<\/jats:italic> KO mice were significantly lower than those in <jats:italic>ADAMTS1<\/jats:italic><jats:sup>flox\/flox<\/jats:sup> mice (45.5\u00a0<jats:italic>versus<\/jats:italic> 81.8% and 18.2\u00a0<jats:italic>versus<\/jats:italic> 42.4%, respectively). Aortas from BAPN\u2010treated <jats:italic>ADAMTS1<\/jats:italic><jats:sup>flox\/flox<\/jats:sup> mice displayed profound destruction of the elastic lamellae, abundant neutrophil and macrophage accumulation in the adventitia, obviously increased neutrophil proportions in peripheral blood and significantly increased expression of inflammatory factors in the early stage of TAAD induction, all of which were markedly suppressed in <jats:italic>ADAMTS1<\/jats:italic> KO mice. Furthermore, <jats:italic>ADAMTS1<\/jats:italic>\u2010deficient macrophages exhibited abrogated migration capacity both <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. In conclusion, <jats:italic>ADAMTS1<\/jats:italic> plays a crucial role in postnatal TAAD formation and rupture by regulating inflammatory responses, suggesting that <jats:italic>ADAMTS1<\/jats:italic> might be a new therapeutic target for TAAD.<\/jats:p><\/jats:sec>","DOI":"10.1113\/ep087018","type":"journal-article","created":{"date-parts":[[2018,9,7]],"date-time":"2018-09-07T07:54:14Z","timestamp":1536306854000},"page":"1717-1731","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Postnatal deficiency of <i>ADAMTS1<\/i> ameliorates thoracic aortic aneurysm and dissection in mice"],"prefix":"10.1113","volume":"103","author":[{"given":"Shanshan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cardiology, China\u2010Japan Friendship School of Clinical Medicine, Peking Union Medical College Chinese Academy of Medical Sciences  Beijing 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