{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T19:55:54Z","timestamp":1793476554772,"version":"4.5.0"},"reference-count":75,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["NIH R35 HL135765"],"award-info":[{"award-number":["NIH R35 HL135765"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["DFG HE 8679\/1-1"],"award-info":[{"award-number":["DFG HE 8679\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011012","name":"Society for Thrombosis and Haemostasis Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011012","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Physician Scientist Program of the Helmholtz-Institute for Translational AngioCardioScience"},{"DOI":"10.13039\/100007569","name":"Carl Zeiss Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007569","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003042","name":"Else-Kr\u00f6hner Fresenius Stiftung","doi-asserted-by":"publisher","award":["2023_EKSE.46"],"award-info":[{"award-number":["2023_EKSE.46"]}],"id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010447","name":"German Research Centre for Cardiovascular Research","doi-asserted-by":"publisher","award":["FKZ81Z0700110"],"award-info":[{"award-number":["FKZ81Z0700110"]}],"id":[{"id":"10.13039\/100010447","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010447","name":"German Research Centre for Cardiovascular Research","doi-asserted-by":"publisher","award":["394046768"],"award-info":[{"award-number":["394046768"]}],"id":[{"id":"10.13039\/100010447","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Berta-Ottenstein-Programme"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Diabetes is associated with increased risk of cardiovascular and renal disease. This study investigated the role of peptidylarginine deiminase 4 (PAD4), neutrophil extracellular traps (NETs), and inflammasome activation in diabetic cardiomyopathy (DCM) and kidney disease (DKD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Endomyocardial biopsies (EMB) from heart failure (HF) patients (n = 20) with or without diabetes were stained for NETs. Wild-type (WT) and PAD4\u207b\/\u207b mice were subjected to streptozotocin (STZ)-induced diabetes and cardiac function, blood glucose, body weight, and exercise tolerance were assessed longitudinally. NETosis and ASC specks were evaluated in mouse and human neutrophils. Cardiac and renal fibrosis was assessed by Sirius Red\/Fast Green staining. Confocal microscopy, ELISA, and flow cytometry were used to quantify NETs, IL-1\u03b2, von Willebrand factor (VWF), cytokine transforming growth factor beta-1 (TGF-\u03b21), and neutrophil infiltration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Myocardial NET burden was increased in HF patients with diabetes. High glucose triggered inflammasome activation in human neutrophils. After STZ, PAD4\u207b\/\u207b and WT mice developed hyperglycaemia and weight loss, yet only WT neutrophils showed increased NETosis and ASC speck formation. Only diabetic WT mice exhibited elevated IL-1\u03b2 and VWF levels, impaired cardiac function, reduced exercise tolerance, and pulmonary oedema; PAD4\u207b\/\u207b mice were protected. Wild-type diabetic hearts and kidneys showed greater fibrosis, neutrophil infiltration, NETs, and TGF-\u03b21 levels. Kidney injury in WT mice was reflected by albuminuria and renal fibrosis, whereas PAD4\u207b\/\u207b mice preserved renal function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Diabetes promotes neutrophil inflammasome activation and NETosis, driving cardiac and renal inflammation and fibrosis. Peptidylarginine deiminase 4 deficiency prevents heart failure and preserves kidney function in experimental diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehaf963","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T12:55:45Z","timestamp":1763038545000},"source":"Crossref","is-referenced-by-count":16,"title":["Neutrophil extracellular traps and peptidylarginine deiminase 4\u2013mediated inflammasome activation link diabetes to cardiorenal injury and heart failure"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9568-9426","authenticated-orcid":false,"given":"Nicolas","family":"Schommer","sequence":"first","affiliation":[{"name":"Program in Cellular and Molecular Medicine, Boston Children\u2019s Hospital , 1 Blackfan Circle Boston, MA 02115 ,","place":["USA"]},{"name":"Cardiology, Haemostaseology, and Medical Intensive Care, Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University , Mannheim ,","place":["Germany"]},{"name":"Helmholtz-Institute for Translational AngioCardioScience (HI-TAC) of the Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association (MDC), Heidelberg University , Heidelberg ,","place":["Germany"]},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg\/Mannheim ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4852-4738","authenticated-orcid":false,"given":"Nicolas","family":"Gendron","sequence":"additional","affiliation":[{"name":"Program in Cellular and Molecular Medicine, Boston Children\u2019s Hospital , 1 Blackfan Circle Boston, MA 02115 ,","place":["USA"]},{"name":"Department of Pediatrics, Harvard Medical School , 25 Shattuck Street, Boston, MA 02115 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Partner Site Heidelberg\/Mannheim ,","place":["Germany"]},{"name":"European Center for AngioScience (ECAS), Medical Faculty Mannheim, University of Heidelberg , Mannheim ,","place":["Germany"]},{"name":"Cardiovascular Systems Biology, Medical Faculty Mannheim, University of Heidelberg , Mannheim ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Duerschmied","sequence":"additional","affiliation":[{"name":"Cardiology, Haemostaseology, and Medical Intensive Care, Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University , Mannheim ,","place":["Germany"]},{"name":"Helmholtz-Institute for Translational AngioCardioScience (HI-TAC) of the Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association (MDC), Heidelberg University , Heidelberg ,","place":["Germany"]},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg\/Mannheim ,","place":["Germany"]},{"name":"European Center for 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