{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T20:37:21Z","timestamp":1793824641869,"version":"4.6.1"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"18","license":[{"start":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T00:00:00Z","timestamp":1714089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82130010"],"award-info":[{"award-number":["82130010"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Shanghai Science and Technology Commission","doi-asserted-by":"crossref","award":["22JC1400500"],"award-info":[{"award-number":["22JC1400500"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003399","name":"Shanghai Science and Technology Commission","doi-asserted-by":"crossref","award":["81873495"],"award-info":[{"award-number":["81873495"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003399","name":"Shanghai Science and Technology Commission","doi-asserted-by":"crossref","award":["82171569"],"award-info":[{"award-number":["82171569"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Heart Failure Center Research Foundation of Fujian Provincial Hospital","id":[{"id":"https:\/\/ror.org\/045wzwx52","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Minhang District Science Committee of Shanghai","award":["2022MHZ042"],"award-info":[{"award-number":["2022MHZ042"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>The Glu504Lys polymorphism in the aldehyde dehydrogenase 2 (ALDH2) gene is closely associated with myocardial ischaemia\/reperfusion injury (I\/RI). The effects of ALDH2 on neutrophil extracellular trap (NET) formation (i.e. NETosis) during I\/RI remain unknown. This study aimed to investigate the role of ALDH2 in NETosis in the pathogenesis of myocardial I\/RI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The mouse model of myocardial I\/RI was constructed on wild-type, ALDH2 knockout, peptidylarginine deiminase 4 (Pad4) knockout, and ALDH2\/PAD4 double knockout mice. Overall, 308 ST-elevation myocardial infarction patients after primary percutaneous coronary intervention were enrolled in the study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Enhanced NETosis was observed in human neutrophils carrying the ALDH2 genetic mutation and ischaemic myocardium of ALDH2 knockout mice compared with controls. PAD4 knockout or treatment with NETosis-targeting drugs (GSK484, DNase1) substantially attenuated the extent of myocardial damage, particularly in ALDH2 knockout. Mechanistically, ALDH2 deficiency increased damage-associated molecular pattern release and susceptibility to NET-induced damage during myocardial I\/RI. ALDH2 deficiency induced NOX2-dependent NETosis via upregulating the endoplasmic reticulum stress\/microsomal glutathione S-transferase 2\/leukotriene C4 (LTC4) pathway. The Food and Drug Administration-approved LTC4 receptor antagonist pranlukast ameliorated I\/RI by inhibiting NETosis in both wild-type and ALDH2 knockout mice. Serum myeloperoxidase\u2013DNA complex and LTC4 levels exhibited the predictive effect on adverse left ventricular remodelling at 6 months after primary percutaneous coronary intervention in ST-elevation myocardial infarction patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>ALDH2 deficiency exacerbates myocardial I\/RI by promoting NETosis via the endoplasmic reticulum stress\/microsomal glutathione S-transferase 2\/LTC4\/NOX2 pathway. This study hints at the role of NETosis in the pathogenesis of myocardial I\/RI, and pranlukast might be a potential therapeutic option for attenuating I\/RI, particularly in individuals with the ALDH2 mutation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehae205","type":"journal-article","created":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T03:17:19Z","timestamp":1711509439000},"page":"1662-1680","source":"Crossref","is-referenced-by-count":106,"title":["Myocardial reperfusion injury exacerbation due to ALDH2 deficiency is mediated by neutrophil extracellular traps and prevented by leukotriene C4 inhibition"],"prefix":"10.1093","volume":"45","author":[{"given":"Kun","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases , 180 Fenglin Road, Shanghai 200032 , 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Fifth People\u2019s Hospital of Shanghai, Fudan University , 128 Ruili Road, Shanghai 200240 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaran","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Lihuili Hospital Facilitated to Ningbo University , 57 Xingning Road, Ningbo 315040 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinyin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiology, Zhongshan Hospital, Fudan University , 180 Fenglin Road, Shanghai 200032 , China"},{"name":"Department of Medical Imaging, Fudan University , 180 Fenglin Road, Shanghai 200032 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital , 134 Dongjie Road, Fuzhou 350001 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4376-2390","authenticated-orcid":false,"given":"Juntao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology, Zhongshan Hospital, Fudan University , 180 Fenglin Road, Shanghai 200032 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Lyu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Fifth People\u2019s Hospital of Shanghai, Fudan University , 128 Ruili Road, Shanghai 200240 , 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Cardiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital , 134 Dongjie Road, Fuzhou 350001 , China"},{"name":"Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Provincial Center for Geriatrics, Fujian Provincial Clinical Research Center for Severe Acute Cardiovascular Diseases , 134 Dongjie Road, Fuzhou 350001 , China"},{"name":"Fujian Heart Failure Center Alliance , 134 Dongjie Road, Fuzhou 350001 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9360-7332","authenticated-orcid":false,"given":"Junbo","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases , 180 Fenglin Road, Shanghai 200032 , China"},{"name":"Institutes of Biomedical Sciences, Fudan University , 131 Dongan Road, Shanghai 200032 , China"},{"name":"Key Laboratory of Viral Heart Diseases, 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