{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T23:14:11Z","timestamp":1793229251298,"version":"4.5.0"},"reference-count":74,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T00:00:00Z","timestamp":1628553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31872739 to K.C., 81602763 to X.T., 81703132 to Z.W."],"award-info":[{"award-number":["31872739 to K.C., 81602763 to X.T., 81703132 to Z.W."]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"publisher","award":["(2018ZX09303006-001-006 to J.L. and 2019ZX09201004-003 to J.L.)"],"award-info":[{"award-number":["(2018ZX09303006-001-006 to J.L. and 2019ZX09201004-003 to J.L.)"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]},{"name":"China Postdoctoral Science Foundation funded project"},{"DOI":"10.13039\/100012551","name":"Applied Basic Research Program of Sichuan Province","doi-asserted-by":"publisher","award":["(2021YJ0420 to Z.W.)"],"award-info":[{"award-number":["(2021YJ0420 to Z.W.)"]}],"id":[{"id":"10.13039\/100012551","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Postdoctoral Fund for West China Hospital","award":["(2019HXBH075 to Z.W.)"],"award-info":[{"award-number":["(2019HXBH075 to Z.W.)"]}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>After myocardial infarction (MI), injured cardiomyocytes recruit neutrophils and monocytes\/macrophages to myocardium, which in turn initiates inflammatory and reparative cascades, respectively. Either insufficient or excessive inflammation impairs cardiac healing. As an endogenous inhibitor of neutrophil adhesion, EDIL3 plays a crucial role in inflammatory regulation. However, the role of EDIL3 in MI remains obscure. We aimed to define the role of EDIL3 in cardiac remodelling after MI.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Serum EDIL3 levels in MI patients were negatively associated with MI biomarkers. Consistently, WT mice after MI showed low levels of cardiac EDIL3. Compared with WT mice, Edil3\u2212\/\u2212 mice showed improvement of post-MI adverse remodelling, as they exhibited lower mortality, better cardiac function, shorter scar length, and smaller LV cavity. Accordingly, infarcted hearts of Edil3\u2212\/\u2212 mice contained fewer cellular debris and lower amounts of fibrosis content, with decreased collagen I\/III expression and the percentage of \u03b1-smooth muscle actin myofibroblasts. Mechanistically, EDIL3 deficiency did not affect the recruitment of monocytes or T cells, but enhanced neutrophil recruitment and following expansion of pro-inflammatory Mertk\u2212MHC-IIlo-int (myeloid-epithelial-reproductive tyrosine kinase\/major histocompatibility complex II) macrophages. The injection of neutrophil-specific C-X-C motif chemokine receptor 2 antagonist eliminated the differences in macrophage polarization and cardiac function between WT and Edil3\u2212\/\u2212 mice after MI. Neutrophil extracellular traps (NETs), which were more abundant in the hearts of Edil3\u2212\/\u2212 mice, contributed to Mertk\u2212MHC-IIlo-int polarization via Toll-like receptor 9 pathway. The inhibition of NET formation by treatment of neutrophil elastase inhibitor or DNase I impaired macrophage polarization, increased cellular debris and aggravated cardiac adverse remodelling, thus removed the differences of cardiac function between WT and Edil3\u2212\/\u2212 mice. Totally, EDIL3 plays an important role in NET-primed macrophage polarization and cardiac remodelling during MI.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>We not only reveal that EDIL3 deficiency ameliorates adverse cardiac healing via NET-mediated pro-inflammatory macrophage polarization but also discover a new crosstalk between neutrophil and macrophage after MI.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvab269","type":"journal-article","created":{"date-parts":[[2021,8,8]],"date-time":"2021-08-08T19:09:47Z","timestamp":1628449787000},"page":"2179-2195","source":"Crossref","is-referenced-by-count":97,"title":["EDIL3 deficiency ameliorates adverse cardiac remodelling by neutrophil extracellular traps (NET)-mediated macrophage polarization"],"prefix":"10.1093","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7576-4820","authenticated-orcid":false,"given":"Xiaoqiong","family":"Wei","sequence":"first","affiliation":[{"name":"State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy , 1 Keyuan 4th Road, Gaopeng Street, Chengdu, Sichuan 610041 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7219-3425","authenticated-orcid":false,"given":"Song","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, West China Hospital, Sichuan University , 37 Guoxue Road, Chengdu, Sichuan 610041 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3909-166X","authenticated-orcid":false,"given":"Zhonghui","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Cardiology, West China Hospital, Sichuan University , 37 Guoxue Road, Chengdu, Sichuan 610041 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2516-4752","authenticated-orcid":false,"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy , 1 Keyuan 4th Road, Gaopeng Street, Chengdu, Sichuan 610041 , China"},{"name":"Department of Liver Surgery & Liver Transplantation, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy , 37 Guo Xue Road, Chengdu, Sichuan 610041 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nongyu","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation 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