{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T16:06:54Z","timestamp":1792858014052,"version":"4.5.0"},"reference-count":59,"publisher":"Wiley","issue":"25","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"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":["82373886"],"award-info":[{"award-number":["82373886"]}],"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":["82321005"],"award-info":[{"award-number":["82321005"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013313","name":"Overseas Expertise Introduction Project for Discipline Innovation","doi-asserted-by":"publisher","award":["G20582017001"],"award-info":[{"award-number":["G20582017001"]}],"id":[{"id":"10.13039\/501100013313","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017684","name":"Foundation Research Project of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20253058"],"award-info":[{"award-number":["BK20253058"]}],"id":[{"id":"10.13039\/501100017684","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010035","name":"Outstanding Youth Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20250097"],"award-info":[{"award-number":["BK20250097"]}],"id":[{"id":"10.13039\/501100010035","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":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Myocardial ischemia\u2010reperfusion (MI\/R) injury remains a critical challenge in cardiovascular therapeutics, with metabolic\u2010inflammatory signaling axis emerging as a critical mediator of pathological outcomes. Yet, the specific metabolic pathways interplay with inflammation to exacerbate MI\/R injury remain poorly defined. Here we verify that NETosis of neutrophils is an initiative and causal factor in driving MI\/R injury, specifically, platelet activating factor (PAF) secreted by cardiomyocytes during MI\/R, drives neutrophil extracellular traps (NETs) formation and subsequent NETosis. Increased expression of PAF synthesis enzyme PLA2G6 explains excessive production of PAF. PAF\u2010induced NETosis requires gasdermin D (GSDMD) mediated pore\u2010forming to facilitate NETs extrusion. Both inhibiting NETs and PAF synthesis significantly alleviate MI\/R injury. We further identify dapagliflozin as a potent NETosis inhibitor that protects mice from MI\/R injury in a sodium\u2010glucose co\u2010transporter 2 (SGLT2)\u2010independent manner, which targets neutrophil gelatinase\u2010associated lipocalin\u20102 (LCN2). Notably, increased serum PAF concentration in acute myocardial infarction patients with percutaneous coronary intervention was positively correlated with NETosis and myocardial injury indexes. Of interest, patients receiving dapagliflozin exhibited attenuated myocardial injury in comparison to those without dapagliflozin. Collectively, our study demonstrates PAF serves as a danger signal in triggering NETosis in early MI\/R injury, and manipulating PAF\u2010NETosis signal by dapagliflozin or LCN2 inhibitor might be effective in combating MI\/R injury.<\/jats:p>","DOI":"10.1002\/advs.202519140","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T12:34:58Z","timestamp":1772973298000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["PAF Triggered Pyroptotic NETosis Aggravates Myocardial Ischemia\/Reperfusion Injury"],"prefix":"10.1002","volume":"13","author":[{"given":"Jiawei","family":"Wu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing P. R. China"},{"name":"Department of Gastroenterology Kunshan Hospital Affiliated to Jiangsu University  Kunshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shule","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing P. R. China"},{"name":"Jiangsu Provincial Key Laboratory of Targetome and Innovative Drugs Institute of Innovative Drug China Pharmaceutical University  Nanjing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruofan","family":"Du","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing P. R. China"},{"name":"Jiangsu Provincial Key Laboratory of Targetome and Innovative Drugs Institute of Innovative Drug China Pharmaceutical University  Nanjing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guodong","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing P. R. China"},{"name":"Jiangsu Provincial Key Laboratory of Targetome and Innovative Drugs Institute of Innovative Drug China Pharmaceutical University  Nanjing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Cardiology Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haochi","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing P. R. China"},{"name":"Jiangsu Provincial Key Laboratory of Targetome and Innovative Drugs Institute of Innovative Drug China Pharmaceutical University  Nanjing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqing","family":"Xie","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing P. R. China"},{"name":"Jiangsu Provincial Key Laboratory of Targetome and Innovative Drugs Institute of Innovative Drug China Pharmaceutical University  Nanjing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"He","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing P. R. China"},{"name":"Jiangsu Provincial Key Laboratory of Targetome and Innovative Drugs Institute of Innovative Drug China Pharmaceutical University  Nanjing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyong","family":"Sun","sequence":"additional","affiliation":[{"name":"Jiangsu Provincial Key Laboratory of Targetome and Innovative Drugs Institute of Innovative Drug China Pharmaceutical University  Nanjing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiping","family":"Hao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing P. R. China"},{"name":"Jiangsu Provincial Key Laboratory of Targetome and Innovative Drugs Institute of Innovative Drug China Pharmaceutical University  Nanjing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3834-5018","authenticated-orcid":false,"given":"Lijuan","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing P. R. China"},{"name":"Jiangsu Provincial Key Laboratory of Targetome and Innovative Drugs Institute of Innovative Drug China Pharmaceutical University  Nanjing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI62874"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra071667"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2016.5"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2507"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/9929687"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.318629"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.09.086"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.036044"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010cellbio\u2010020520\u2010111016"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.120158"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.120.314491"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021013097"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27841"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2017.08.014"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/biof.1928"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.12.132"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201800401"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190111"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/cgt.2015.21"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dci.2020.103768"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201016043\u20109"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prostaglandins.2020.106522"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933\u2010017\u20100510\u20101"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12572"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010021\u201003819\u20102"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.02.032"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht090"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(12)60916\u20107"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1195491"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010immunol\u2010030409\u2010101323"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw002"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2014.28"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvy145"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1707914"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13920"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016080925"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.309692"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2100593"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa8064"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3887"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2021.08.014"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1258\/ebm.2011.010316"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aar6676"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aar6689"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504720"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611925"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1812389"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1600827"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2206286"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2023.108385"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dci.2024.105151"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12879\u2010025\u201011119\u20107"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29919"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.223925"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.3791\/58114"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201009046\u20108"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201028492\u20105"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20104939\u20108570\u20108_4"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.3791\/59052"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202519140","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202519140","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202519140","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T08:47:14Z","timestamp":1777884434000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202519140"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,25]]},"references-count":59,"journal-issue":{"issue":"25","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/advs.202519140"],"URL":"https:\/\/doi.org\/10.1002\/advs.202519140","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,25]]},"assertion":[{"value":"2025-10-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e19140"}}