{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T20:16:54Z","timestamp":1784924214661,"version":"3.55.0"},"reference-count":36,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81900418"],"award-info":[{"award-number":["81900418"]}],"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":["82270505"],"award-info":[{"award-number":["82270505"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014761","name":"Natural Science Foundation of Qingdao Municipality","doi-asserted-by":"publisher","award":["23\u20102\u20101\u2010194\u2010zyyd\u2010jch"],"award-info":[{"award-number":["23\u20102\u20101\u2010194\u2010zyyd\u2010jch"]}],"id":[{"id":"10.13039\/501100014761","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:bold>Background<\/jats:bold>\n                    : Thoracic aortic dissection (TAD) is a lethal vascular emergency lacking targeted therapies. Fibroblast activation protein (FAP), a protease implicated in tissue remodeling, exhibits unknown roles in TAD pathogenesis.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods<\/jats:bold>\n                    : Human TAD specimens and \u03b2\u2010aminopropionitrile\u2010induced TAD models were used to assess FAP expression. Global and fibroblast\u2010specific Fap knockout mice were generated to evaluate biological effects of FAP. Bulk and single\u2010cell RNA sequencing were used to map cellular crosstalk and dysregulated signaling pathways. A combination of pharmacological inhibition (Ac\u2010Gly\u2010BoroPro), surface plasmon resonance (SPR), co\u2010immunoprecipitation (co\u2010IP), and functional rescue experiments was utilized to dissect the enzymatic versus nonenzymatic functions of FAP and its interaction with PLAUR\/ITGB1 signaling.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results<\/jats:bold>\n                    : Fibroblast\u2010derived FAP was significantly upregulated in TAD lesions. Fap deletion markedly attenuated inflammatory infiltration, extracellular matrix degradation, and TAD incidence. Surprisingly, pharmacological inhibition of FAP's enzymatic activity failed to protect against TAD. SPR, co\u2010IP, and functional assays revealed that FAP binds directly to macrophage PLAUR via nonenzymatic sites. This interaction triggers ITGB1\/FAK signaling, promoting a pro\u2010inflammatory macrophage phenotype that drives TAD progression.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion<\/jats:bold>\n                    : This study demonstrates that FAP promotes TAD through a nonenzymatic mechanism involving fibroblast\u2010macrophage crosstalk via the FAP\/PLAUR\/ITGB1\/FAK axis. Targeting this pathway might offer a promising therapeutic strategy for TAD.\n                  <\/jats:p>","DOI":"10.1002\/advs.202514786","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T08:45:44Z","timestamp":1770885944000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Fibroblast Activation Protein Promotes Thoracic Aortic Dissection via PLAUR\/ITGB1\u2010Mediated Pro\u2010inflammatory Macrophage Polarization"],"prefix":"10.1002","volume":"13","author":[{"given":"Hongqiao","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Vascular Surgery Shanghai General Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianlie","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Nursing Shanghai General Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery Shanghai General Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Pei","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery Shanghai Fourth People's Hospital School of Medicine Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaiping","family":"Jing","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery Shanghai Fourth People's Hospital School of Medicine Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery The First Affiliated Hospital Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery Shanghai General Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2286-2791","authenticated-orcid":false,"given":"Junjun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery Shanghai General Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehae179"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.058133"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aai8524"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.14712\/fb2009055030077"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fob.2013.12.001"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehq519"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202411152"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.03.018"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2006.11.006"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555\u2010020\u201009909\u20103"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2016.05.093"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M511112200"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108252"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201009453\u2010x"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201015\u20102973"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2017.153"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1387\/ijdb.11330865"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20122344"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2021109470"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2015.08.016"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.122.320781"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102005\u201008\u20103452"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2013.04.048"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C500092200"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi900257m"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvaa142"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.122"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207730"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/23.10.1593"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2017.3224"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756\u20109966\u201033\u201034"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964\u2010023\u201001343\u20106"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010021\u201003823\u20104"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201008008\u20105"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI142468"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.517391"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202514786","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202514786","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202514786","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T10:25:46Z","timestamp":1776939946000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202514786"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,12]]},"references-count":36,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/advs.202514786"],"URL":"https:\/\/doi.org\/10.1002\/advs.202514786","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,12]]},"assertion":[{"value":"2025-08-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14786"}}