{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T09:50:31Z","timestamp":1785750631544,"version":"3.56.0"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T00:00:00Z","timestamp":1653523200000},"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":["81570426"],"award-info":[{"award-number":["81570426"]}],"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":["81500365"],"award-info":[{"award-number":["81500365"]}],"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":["7172040"],"award-info":[{"award-number":["7172040"]}],"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":[[2022,6]]},"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>What is the relationship of chemokine (C\u2010C motif) ligand 8 (CCL8) to thoracic aortic aneurysm and dissection (TAAD) formation in postnatal mice with vascular smooth muscle cell (VSMC) <jats:italic>Tgfbr2<\/jats:italic> disruption, and is dexamethasone a potential treatment?<\/jats:p><\/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>CCL8 was associated with the formation of TAAD in VSMC <jats:italic>Tgfbr2<\/jats:italic>\u2010disrupted mice. Dexamethasone reduced TAAD formation and inhibited mitogen\u2010activated protein kinase (p\u2010p38) and nuclear factor\u2010\u03baB (p\u2010p65) signalling pathways. CCL8 might be an important promoter of aortic inflammation. Dexamethasone provided potential therapeutic effects in TAAD treatment.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Aortic inflammation plays a vital role in initiation and progression of thoracic aortic aneurysm and dissection (TAAD). Disturbance of the transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2) signalling pathway is believed to be one of the pathogenic mechanisms of TAAD. Initially, <jats:italic>Myh11\u2010CreER<jats:sup>T2<\/jats:sup>.Tgfbr2<jats:sup>f\/f<\/jats:sup><\/jats:italic> male mice were used to build a TAAD mouse model, and bioinformatic analyses revealed enriched inflammatory signal pathways and upregulated chemokine (C\u2010C motif) ligand 8 (CCL8). So we hypothesized that vascular smooth muscle cell (VSMC) <jats:italic>Tgfbr2<\/jats:italic> disruption in postnatal mice results in aortic inflammation associated with CCL8 secretion. Real\u2010time quantitative PCR and serum enzyme\u2010linked immunosorbent assay (ELISA) results confirmed that CCL8 expression began to increase after VSMC <jats:italic>Tgfbr2<\/jats:italic> disruption. Next, we cultured mouse thoracic aortas <jats:italic>ex vivo<\/jats:italic>, and observed that the protein expression of CCL8 in culture supernatants was increased by ELISA. Subsequently, the co\u2010localization of CCL8 with \u03b1\u2010smooth muscle actin or CD68 was found to be significantly increased by immunofluorescence. Then, dexamethasone (DEX) was used to treat TAAD in VSMC <jats:italic>Tgfbr2\u2010<\/jats:italic>disrupted mice; the results of histochemical, immunofluorescence and immunohistochemical staining indicated that DEX therapy reduced CCL8 secretion, inflammatory cell recruitment, aortic medial thickening, elastic fibre fragmentation, extracellular matrix degradation and contractile apparatus impairment, and thereby ameliorated TAAD formation. Western blotting showed that mitogen\u2010activated protein kinase and nuclear factor\u2010\u03baB signalling pathways in aorta were overactivated after VSMC <jats:italic>Tgfbr2<\/jats:italic> disruption, but inhibited by DEX therapy. Altogether, CCL8 might be an important promoter in TAAD formation of VSMC <jats:italic>Tgfbr2<\/jats:italic>\u2010disrupted mice, and DEX provided potential therapeutic effects in TAAD treatment.<\/jats:p><\/jats:sec>","DOI":"10.1113\/ep090190","type":"journal-article","created":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T16:52:52Z","timestamp":1648486372000},"page":"631-645","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Dexamethasone attenuated thoracic aortic aneurysm and dissection in vascular smooth muscle cell <i>Tgfbr2<\/i>\u2010disrupted mice with CCL8 suppression"],"prefix":"10.1113","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7555-4185","authenticated-orcid":false,"given":"Xipeng","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Vascular Surgery Peking University People's Hospital  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingle","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery Peking University People's Hospital  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery Peking University People's Hospital  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery Peking University People's Hospital  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Anzhen Hospital Capital Medical University Beijing Institute of Heart Lung and Blood Vessel Disease  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery Peking University People's Hospital  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery Peking University People's Hospital  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjun","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery Peking University People's Hospital  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Anzhen Hospital Capital Medical University Beijing Institute of Heart Lung and Blood Vessel Disease  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery Peking University People's Hospital  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8802"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2010.259"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14137"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/09168451.2020.1762160"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.575765"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1210200110"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2005.09.018"},{"issue":"5","key":"e_1_2_9_9_1","first-page":"1208","article-title":"Matrix metalloproteinase\u20109 (92\u2010kd gelatinase\/type IV collagenase equals gelatinase B) can degrade arterial elastin","volume":"145","author":"Katsuda S.","year":"1994","journal-title":"American Journal of Pathology"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.4110\/in.2009.9.3.90"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.097097"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI69942"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8101227"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1511"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.103104"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1116"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4266"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/1274034"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3791\/59013"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2021.112703"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2010.10.006"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejvs.2019.10.014"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1335"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms160511213"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2017.12.002"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2018.05.246"}],"container-title":["Experimental Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/EP090190","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/EP090190","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/EP090190","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T11:19:10Z","timestamp":1692875950000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/EP090190"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,26]]},"references-count":25,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,6]]}},"alternative-id":["10.1113\/EP090190"],"URL":"https:\/\/doi.org\/10.1113\/ep090190","archive":["Portico"],"relation":{},"ISSN":["0958-0670","1469-445X"],"issn-type":[{"value":"0958-0670","type":"print"},{"value":"1469-445X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,26]]},"assertion":[{"value":"2021-11-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}