{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:57:08Z","timestamp":1791669428968,"version":"4.3.4"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T00:00:00Z","timestamp":1619136000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T00:00:00Z","timestamp":1619136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["SFB-F54"],"award-info":[{"award-number":["SFB-F54"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"name":"B\u00fcrgermeister-Fonds"},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"name":"State of Bavaria, Germany"},{"name":"Ludwig-Maximilians-Universit\u00e4t","award":["LMUinnovativ"],"award-info":[{"award-number":["LMUinnovativ"]}]},{"DOI":"10.13039\/501100005788","name":"Medical University of Vienna","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005788","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Basic Res Cardiol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Upon activation, neutrophils release neutrophil extracellular traps (NETs), which contribute to circulating DNA burden and thrombosis, including ST-segment elevation myocardial infarction (STEMI). Deoxyribonuclease (DNase) 1 degrades circulating DNA and NETs. Lower DNase activity correlates with NET burden and infarct size. The DNase 1 Q222R single nucleotide polymorphism (SNP), impairing DNase 1 function, is linked with myocardial infarction. We assessed whether the Q222R SNP is connected to increased NET burden in STEMI and influences long-term outcomes. We enrolled 711 STEMI patients undergoing primary percutaneous coronary intervention (pPCI), and 1422 controls. Genotyping was performed for DNase 1 Q222R SNP. DNase activity, double-stranded (ds)DNA and citrullinated histone H3 were determined in culprit site and peripheral plasma during pPCI. The association of the Q222R variant on cardiovascular and all-cause mortality was assessed by multivariable Cox regression adjusted for cardiovascular risk factors. Homozygous Q222R DNase 1 variant was present in 64 (9.0%) STEMI patients, at the same frequency as in controls. Patients homozygous for Q222R displayed less DNase activity and increased circulating DNA burden. In overall patients, median survival was 60\u00a0months. Homozygous Q222R variant was independently associated with cardiovascular and all-cause mortality after STEMI. dsDNA\/DNase ratio independently predicted cardiovascular and all-cause mortality. These findings highlight that the Q222R DNase 1 SNP is associated with increased NET burden and decreased compensatory DNase activity, and may serve as an independent risk factor for poor outcome after STEMI.<\/jats:p>","DOI":"10.1007\/s00395-021-00864-w","type":"journal-article","created":{"date-parts":[[2021,4,24]],"date-time":"2021-04-24T23:19:28Z","timestamp":1619306368000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Deoxyribonuclease 1 Q222R single nucleotide polymorphism and long-term mortality after acute myocardial infarction"],"prefix":"10.1007","volume":"116","author":[{"given":"Thomas M.","family":"Hofbauer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Mangold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna S.","family":"Ondracek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adelheid","family":"Panzenb\u00f6ck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Scherz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Distelmaier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Seidl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Kastl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"M\u00fcller-Nurasyid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Peters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin","family":"Strauch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Winker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyne","family":"Wohlschl\u00e4ger-Krenn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Nistler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0485-2692","authenticated-orcid":false,"given":"Irene M.","family":"Lang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,23]]},"reference":[{"key":"864_CR1","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1111\/j.1538-7836.2011.04422.x","volume":"9","author":"CT Ammollo","year":"2011","unstructured":"Ammollo CT, Semeraro F, Xu J, Esmon NL, Esmon CT (2011) Extracellular histones increase plasma thrombin generation by impairing thrombomodulin-dependent protein C activation. J Thromb Haemost 9:1795\u20131803. https:\/\/doi.org\/10.1111\/j.1538-7836.2011.04422.x","journal-title":"J Thromb Haemost"},{"key":"864_CR2","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/0167-5273(93)90203-S","volume":"38","author":"AE Aranega","year":"1993","unstructured":"Aranega AE, Reina A, Muros MA, Alvarez L, Prados J, Aranega A (1993) Circulating alpha-actin protein in acute myocardial infarction. Int J Cardiol 38:49\u201355","journal-title":"Int J Cardiol"},{"key":"864_CR3","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1016\/0092-8674(78)90277-5","volume":"15","author":"I Blikstad","year":"1978","unstructured":"Blikstad I, Markey F, Carlsson L, Persson T, Lindberg U (1978) Selective assay of monomeric and filamentous actin in cell extracts, using inhibition of deoxyribonuclease I. Cell 15:935\u2013943","journal-title":"Cell"},{"key":"864_CR4","doi-asserted-by":"publisher","first-page":"2032","DOI":"10.1161\/atvbaha.113.301627","volume":"33","author":"JI Borissoff","year":"2013","unstructured":"Borissoff JI, Joosen IA, Versteylen MO, Brill A, Fuchs TA, Savchenko AS, Gallant M, Martinod K, Ten Cate H, Hofstra L, Crijns HJ, Wagner DD, Kietselaer B (2013) Elevated levels of circulating DNA and chromatin are independently associated with severe coronary atherosclerosis and a prothrombotic state. Arterioscler Thromb Vasc Biol 33:2032\u20132040. https:\/\/doi.org\/10.1161\/atvbaha.113.301627","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"864_CR5","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1111\/j.1538-7836.2011.04544.x","volume":"10","author":"A Brill","year":"2012","unstructured":"Brill A, Fuchs TA, Savchenko AS, Thomas GM, Martinod K, De Meyer SF, Bhandari AA, Wagner DD (2012) Neutrophil extracellular traps promote deep vein thrombosis in mice. J Thromb Haemost 10:136\u2013144. https:\/\/doi.org\/10.1111\/j.1538-7836.2011.04544.x","journal-title":"J Thromb Haemost"},{"key":"864_CR6","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.1126\/science.1092385","volume":"303","author":"V Brinkmann","year":"2004","unstructured":"Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Weinrauch Y, Zychlinsky A (2004) Neutrophil extracellular traps kill bacteria. Science 303:1532\u20131535. https:\/\/doi.org\/10.1126\/science.1092385","journal-title":"Science"},{"key":"864_CR7","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1083\/jcb.201203170","volume":"198","author":"V Brinkmann","year":"2012","unstructured":"Brinkmann V, Zychlinsky A (2012) Neutrophil extracellular traps: is immunity the second function of chromatin? J Cell Biol 198:773\u2013783. https:\/\/doi.org\/10.1083\/jcb.201203170","journal-title":"J Cell Biol"},{"key":"864_CR8","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1161\/circulationaha.108.767772","volume":"118","author":"CE Buller","year":"2008","unstructured":"Buller CE, Fu Y, Mahaffey KW, Todaro TG, Adams P, Westerhout CM, White HD, van \u2019t Hof AW, Van de Werf FJ, Wagner GS, Granger CB, Armstrong PW, (2008) ST-segment recovery and outcome after primary percutaneous coronary intervention for ST-elevation myocardial infarction: insights from the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial. Circulation 118:1335\u20131346. https:\/\/doi.org\/10.1161\/circulationaha.108.767772","journal-title":"Circulation"},{"key":"864_CR9","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1136\/hrt.72.1.16","volume":"72","author":"AM Choy","year":"1994","unstructured":"Choy AM, Darbar D, Lang CC, Pringle TH, McNeill GP, Kennedy NS, Struthers AD (1994) Detection of left ventricular dysfunction after acute myocardial infarction: comparison of clinical, echocardiographic, and neurohormonal methods. Br Heart J 72:16\u201322. https:\/\/doi.org\/10.1136\/hrt.72.1.16","journal-title":"Br Heart J"},{"key":"864_CR10","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1016\/j.jcin.2013.05.011","volume":"6","author":"G Crimi","year":"2013","unstructured":"Crimi G, Pica S, Raineri C, Bramucci E, De Ferrari GM, Klersy C, Ferlini M, Marinoni B, Repetto A, Romeo M, Rosti V, Massa M, Raisaro A, Leonardi S, Rubartelli P, Oltrona Visconti L, Ferrario M (2013) Remote ischemic post-conditioning of the lower limb during primary percutaneous coronary intervention safely reduces enzymatic infarct size in anterior myocardial infarction: a randomized controlled trial. JACC Cardiovasc Interv 6:1055\u20131063. https:\/\/doi.org\/10.1016\/j.jcin.2013.05.011","journal-title":"JACC Cardiovasc Interv"},{"key":"864_CR11","doi-asserted-by":"publisher","first-page":"2117","DOI":"10.1016\/j.jacc.2007.06.057","volume":"50","author":"JA de Lemos","year":"2007","unstructured":"de Lemos JA, Morrow DA, Blazing MA, Jarolim P, Wiviott SD, Sabatine MS, Califf RM, Braunwald E (2007) Serial measurement of monocyte chemoattractant protein-1 after acute coronary syndromes: results from the A to Z trial. J Am Coll Cardiol 50:2117\u20132124. https:\/\/doi.org\/10.1016\/j.jacc.2007.06.057","journal-title":"J Am Coll Cardiol"},{"key":"864_CR12","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1161\/circresaha.116.309692","volume":"120","author":"Y Doring","year":"2017","unstructured":"Doring Y, Soehnlein O, Weber C (2017) Neutrophil Extracellular Traps in Atherosclerosis and Atherothrombosis. Circ Res 120:736\u2013743. https:\/\/doi.org\/10.1161\/circresaha.116.309692","journal-title":"Circ Res"},{"key":"864_CR13","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1161\/circresaha.117.312494","volume":"123","author":"G Franck","year":"2018","unstructured":"Franck G, Mawson TL, Folco EJ, Molinaro R, Ruvkun V, Engelbertsen D, Liu X, Tesmenitsky Y, Shvartz E, Sukhova GK, Michel JB, Nicoletti A, Lichtman A, Wagner D, Croce KJ, Libby P (2018) Roles of PAD4 and NETosis in experimental atherosclerosis and arterial injury: implications for superficial erosion. Circ Res 123:33\u201342. https:\/\/doi.org\/10.1161\/circresaha.117.312494","journal-title":"Circ Res"},{"key":"864_CR14","doi-asserted-by":"publisher","first-page":"15880","DOI":"10.1073\/pnas.1005743107","volume":"107","author":"TA Fuchs","year":"2010","unstructured":"Fuchs TA, Brill A, Duerschmied D, Schatzberg D, Monestier M, Myers DD Jr, Wrobleski SK, Wakefield TW, Hartwig JH, Wagner DD (2010) Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci USA 107:15880\u201315885. https:\/\/doi.org\/10.1073\/pnas.1005743107","journal-title":"Proc Natl Acad Sci USA"},{"key":"864_CR15","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1038\/s41598-017-01148-x","volume":"7","author":"E Gaitzsch","year":"2017","unstructured":"Gaitzsch E, Czermak T, Ribeiro A, Heun Y, Bohmer M, Merkle M, Mannell H, Schulz C, Wornle M, Pircher J (2017) Double-stranded DNA induces a prothrombotic phenotype in the vascular endothelium. Sci Rep 7:1112. https:\/\/doi.org\/10.1038\/s41598-017-01148-x","journal-title":"Sci Rep"},{"key":"864_CR16","doi-asserted-by":"publisher","DOI":"10.1007\/s00392-018-1387-z","author":"HE Groot","year":"2018","unstructured":"Groot HE, Al Ali L, van der Horst ICC, Schurer RAJ, van der Werf HW, Lipsic E, van Veldhuisen DJ, Karper JC, van der Harst P (2018) Plasma interleukin 6 levels are associated with cardiac function after ST-elevation myocardial infarction. Clin Res Cardiol. https:\/\/doi.org\/10.1007\/s00392-018-1387-z","journal-title":"Clin Res Cardiol"},{"key":"864_CR17","doi-asserted-by":"publisher","first-page":"1916","DOI":"10.1161\/circulationaha.115.018931","volume":"133","author":"A Hartley","year":"2016","unstructured":"Hartley A, Marshall DC, Salciccioli JD, Sikkel MB, Maruthappu M, Shalhoub J (2016) Trends in mortality from ischemic heart disease and cerebrovascular disease in Europe: 1980 to 2009. Circulation 133:1916\u20131926. https:\/\/doi.org\/10.1161\/circulationaha.115.018931","journal-title":"Circulation"},{"key":"864_CR18","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s00395-019-0740-3","volume":"114","author":"TM Hofbauer","year":"2019","unstructured":"Hofbauer TM, Mangold A, Scherz T, Seidl V, Panzenb\u00f6ck A, Ondracek AS, M\u00fcller J, Schneider M, Binder T, Hell L, Lang IM (2019) Neutrophil extracellular traps and fibrocytes in ST-segment elevation myocardial infarction. Basic Res Cardiol 114:33. https:\/\/doi.org\/10.1007\/s00395-019-0740-3","journal-title":"Basic Res Cardiol"},{"issue":"Suppl 1","key":"864_CR19","doi-asserted-by":"publisher","first-page":"S19","DOI":"10.1055\/s-2005-858235","volume":"67","author":"R Holle","year":"2005","unstructured":"Holle R, Happich M, Lowel H, Wichmann HE (2005) KORA\u2013a research platform for population based health research. Gesundheitswesen 67(Suppl 1):S19-25. https:\/\/doi.org\/10.1055\/s-2005-858235","journal-title":"Gesundheitswesen"},{"key":"864_CR20","doi-asserted-by":"publisher","first-page":"e0191150","DOI":"10.1371\/journal.pone.0191150","volume":"13","author":"M Jimenez-Alcazar","year":"2018","unstructured":"Jimenez-Alcazar M, Limacher A, Panda R, Mean M, Bitterling J, Peine S, Renne T, Beer JH, Aujesky D, Lammle B, Fuchs TA (2018) Circulating extracellular DNA is an independent predictor of mortality in elderly patients with venous thromboembolism. PLoS ONE 13:e0191150. https:\/\/doi.org\/10.1371\/journal.pone.0191150","journal-title":"PLoS ONE"},{"key":"864_CR21","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1111\/jth.12796","volume":"13","author":"M Jimenez-Alcazar","year":"2015","unstructured":"Jimenez-Alcazar M, Napirei M, Panda R, Kohler EC, Kremer Hovinga JA, Mannherz HG, Peine S, Renne T, Lammle B, Fuchs TA (2015) Impaired DNase1-mediated degradation of neutrophil extracellular traps is associated with acute thrombotic microangiopathies. J Thromb Haemost 13:732\u2013742. https:\/\/doi.org\/10.1111\/jth.12796","journal-title":"J Thromb Haemost"},{"key":"864_CR22","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.1126\/science.aam8897","volume":"358","author":"M Jimenez-Alcazar","year":"2017","unstructured":"Jimenez-Alcazar M, Rangaswamy C, Panda R, Bitterling J, Simsek YJ, Long AT, Bilyy R, Krenn V, Renne C, Renne T, Kluge S, Panzer U, Mizuta R, Mannherz HG, Kitamura D, Herrmann M, Napirei M, Fuchs TA (2017) Host DNases prevent vascular occlusion by neutrophil extracellular traps. Science 358:1202\u20131206. https:\/\/doi.org\/10.1126\/science.aam8897","journal-title":"Science"},{"key":"864_CR23","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1530\/erp-19-0026","volume":"6","author":"G Joseph","year":"2019","unstructured":"Joseph G, Zaremba T, Johansen MB, Ekeloef S, Heiberg E, Engblom H, Jensen SE, Sogaard P (2019) Echocardiographic global longitudinal strain is associated with infarct size assessed by cardiac magnetic resonance in acute myocardial infarction. Echo Res Pract 6:81\u201389. https:\/\/doi.org\/10.1530\/erp-19-0026","journal-title":"Echo Res Pract"},{"key":"864_CR24","doi-asserted-by":"publisher","first-page":"2398","DOI":"10.1161\/01.cir.0000129232.61483.43","volume":"109","author":"Y Kawai","year":"2004","unstructured":"Kawai Y, Yoshida M, Arakawa K, Kumamoto T, Morikawa N, Masamura K, Tada H, Ito S, Hoshizaki H, Oshima S, Taniguchi K, Terasawa H, Miyamori I, Kishi K, Yasuda T (2004) Diagnostic use of serum deoxyribonuclease I activity as a novel early-phase marker in acute myocardial infarction. Circulation 109:2398\u20132400. https:\/\/doi.org\/10.1161\/01.cir.0000129232.61483.43","journal-title":"Circulation"},{"key":"864_CR25","doi-asserted-by":"publisher","first-page":"2081","DOI":"10.1093\/eurheartj\/ehl177","volume":"27","author":"T Kumamoto","year":"2006","unstructured":"Kumamoto T, Kawai Y, Arakawa K, Morikawa N, Kuribara J, Tada H, Taniguchi K, Tatami R, Miyamori I, Kominato Y, Kishi K, Yasuda T (2006) Association of Gln222Arg polymorphism in the deoxyribonuclease I (DNase I) gene with myocardial infarction in Japanese patients. Eur Heart J 27:2081\u20132087. https:\/\/doi.org\/10.1093\/eurheartj\/ehl177","journal-title":"Eur Heart J"},{"key":"864_CR26","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1002\/ana.24993","volume":"82","author":"E Laridan","year":"2017","unstructured":"Laridan E, Denorme F, Desender L, Francois O, Andersson T, Deckmyn H, Vanhoorelbeke K, De Meyer SF (2017) Neutrophil extracellular traps in ischemic stroke thrombi. Ann Neurol 82:223\u2013232. https:\/\/doi.org\/10.1002\/ana.24993","journal-title":"Ann Neurol"},{"key":"864_CR27","doi-asserted-by":"publisher","first-page":"2004","DOI":"10.1056\/NEJMra1216063","volume":"368","author":"P Libby","year":"2013","unstructured":"Libby P (2013) Mechanisms of acute coronary syndromes and their implications for therapy. N Engl J Med 368:2004\u20132013. https:\/\/doi.org\/10.1056\/NEJMra1216063","journal-title":"N Engl J Med"},{"key":"864_CR28","doi-asserted-by":"publisher","first-page":"11599","DOI":"10.1038\/s41598-019-47853-7","volume":"9","author":"J Liu","year":"2019","unstructured":"Liu J, Yang D, Wang X, Zhu Z, Wang T, Ma A, Liu P (2019) Neutrophil extracellular traps and dsDNA predict outcomes among patients with ST-elevation myocardial infarction. Sci Rep 9:11599. https:\/\/doi.org\/10.1038\/s41598-019-47853-7","journal-title":"Sci Rep"},{"key":"864_CR29","doi-asserted-by":"publisher","first-page":"L586","DOI":"10.1152\/ajplung.00365.2013","volume":"307","author":"L Luo","year":"2014","unstructured":"Luo L, Zhang S, Wang Y, Rahman M, Syk I, Zhang E, Thorlacius H (2014) Proinflammatory role of neutrophil extracellular traps in abdominal sepsis. Am J Physiol Lung Cell Mol Physiol 307:L586-596. https:\/\/doi.org\/10.1152\/ajplung.00365.2013","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"864_CR30","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1161\/circresaha.116.304944","volume":"116","author":"A Mangold","year":"2015","unstructured":"Mangold A, Alias S, Scherz T, Hofbauer T, Jakowitsch J, Panzenbock A, Simon D, Laimer D, Bangert C, Kammerlander A, Mascherbauer J, Winter MP, Distelmaier K, Adlbrecht C, Preissner KT, Lang IM (2015) Coronary neutrophil extracellular trap burden and deoxyribonuclease activity in ST-elevation acute coronary syndrome are predictors of ST-segment resolution and infarct size. Circ Res 116:1182\u20131192. https:\/\/doi.org\/10.1161\/circresaha.116.304944","journal-title":"Circ Res"},{"key":"864_CR31","doi-asserted-by":"publisher","first-page":"16304","DOI":"10.1038\/s41598-019-52671-y","volume":"9","author":"A Mangold","year":"2019","unstructured":"Mangold A, Hofbauer TM, Ondracek AS, Artner T, Scherz T, Speidl WS, Krychtiuk KA, Sadushi-Kolici R, Jakowitsch J, Lang IM (2019) Neutrophil extracellular traps and monocyte subsets at the culprit lesion site of myocardial infarction patients. Sci Rep 9:16304. https:\/\/doi.org\/10.1038\/s41598-019-52671-y","journal-title":"Sci Rep"},{"key":"864_CR32","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1084\/jem.20160530","volume":"214","author":"K Martinod","year":"2017","unstructured":"Martinod K, Witsch T, Erpenbeck L, Savchenko A, Hayashi H, Cherpokova D, Gallant M, Mauler M, Cifuni SM, Wagner DD (2017) Peptidylarginine deiminase 4 promotes age-related organ fibrosis. J Exp Med 214:439\u2013458. https:\/\/doi.org\/10.1084\/jem.20160530","journal-title":"J Exp Med"},{"key":"864_CR33","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1160\/th11-09-0650","volume":"107","author":"RT Megens","year":"2012","unstructured":"Megens RT, Vijayan S, Lievens D, Doring Y, van Zandvoort MA, Grommes J, Weber C, Soehnlein O (2012) Presence of luminal neutrophil extracellular traps in atherosclerosis. Thromb Haemost 107:597\u2013598. https:\/\/doi.org\/10.1160\/th11-09-0650","journal-title":"Thromb Haemost"},{"key":"864_CR34","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.jaut.2015.07.015","volume":"65","author":"M Merkle","year":"2015","unstructured":"Merkle M, Pircher J, Mannell H, Krotz F, Blum P, Czermak T, Gaitzsch E, Schneider C, Koppel S, Ribeiro A, Wornle M (2015) LL37 inhibits the inflammatory endothelial response induced by viral or endogenous DNA. J Autoimmun 65:19\u201329. https:\/\/doi.org\/10.1016\/j.jaut.2015.07.015","journal-title":"J Autoimmun"},{"key":"864_CR35","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1111\/j.1742-4658.2008.06849.x","volume":"276","author":"M Napirei","year":"2009","unstructured":"Napirei M, Ludwig S, Mezrhab J, Klockl T, Mannherz HG (2009) Murine serum nucleases\u2013contrasting effects of plasmin and heparin on the activities of DNase1 and DNase1-like 3 (DNase1l3). Febs j 276:1059\u20131073. https:\/\/doi.org\/10.1111\/j.1742-4658.2008.06849.x","journal-title":"Febs j"},{"key":"864_CR36","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1042\/bj20040046","volume":"380","author":"M Napirei","year":"2004","unstructured":"Napirei M, Ricken A, Eulitz D, Knoop H, Mannherz HG (2004) Expression pattern of the deoxyribonuclease 1 gene: lessons from the Dnase1 knockout mouse. Biochem J 380:929\u2013937. https:\/\/doi.org\/10.1042\/bj20040046","journal-title":"Biochem J"},{"key":"864_CR37","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2021372","author":"SM Nidorf","year":"2020","unstructured":"Nidorf SM, Fiolet ATL, Mosterd A, Eikelboom JW, Schut A, Opstal TSJ, The SHK, Xu XF, Ireland MA, Lenderink T, Latchem D, Hoogslag P, Jerzewski A, Nierop P, Whelan A, Hendriks R, Swart H, Schaap J, Kuijper AFM, van Hessen MWJ, Saklani P, Tan I, Thompson AG, Morton A, Judkins C, Bax WA, Dirksen M, Alings MMW, Hankey GJ, Budgeon CA, Tijssen JGP, Cornel JH, Thompson PL (2020) Colchicine in patients with chronic coronary disease. N Engl J Med. https:\/\/doi.org\/10.1056\/NEJMoa2021372","journal-title":"N Engl J Med"},{"key":"864_CR38","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1038\/nrrheum.2015.151","volume":"12","author":"DS Pisetsky","year":"2016","unstructured":"Pisetsky DS (2016) Anti-DNA antibodies\u2013quintessential biomarkers of SLE. Nat Rev Rheumatol 12:102\u2013110. https:\/\/doi.org\/10.1038\/nrrheum.2015.151","journal-title":"Nat Rev Rheumatol"},{"key":"864_CR39","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1093\/eurheartj\/ehv044","volume":"36","author":"T Quillard","year":"2015","unstructured":"Quillard T, Araujo HA, Franck G, Shvartz E, Sukhova G, Libby P (2015) TLR2 and neutrophils potentiate endothelial stress, apoptosis and detachment: implications for superficial erosion. Eur Heart J 36:1394\u20131404. https:\/\/doi.org\/10.1093\/eurheartj\/ehv044","journal-title":"Eur Heart J"},{"key":"864_CR40","doi-asserted-by":"publisher","first-page":"e32366","DOI":"10.1371\/journal.pone.0032366","volume":"7","author":"M Saffarzadeh","year":"2012","unstructured":"Saffarzadeh M, Juenemann C, Queisser MA, Lochnit G, Barreto G, Galuska SP, Lohmeyer J, Preissner KT (2012) Neutrophil extracellular traps directly induce epithelial and endothelial cell death: a predominant role of histones. PLoS ONE 7:e32366. https:\/\/doi.org\/10.1371\/journal.pone.0032366","journal-title":"PLoS ONE"},{"key":"864_CR41","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.jdermsci.2018.08.010","volume":"92","author":"R Safi","year":"2018","unstructured":"Safi R, Kallas R, Bardawil T, Mehanna CJ, Abbas O, Hamam R, Uthman I, Kibbi AG, Nassar D (2018) Neutrophils contribute to vasculitis by increased release of neutrophil extracellular traps in Beh\u00e7et\u2019s disease. J Dermatol Sci 92:143\u2013150. https:\/\/doi.org\/10.1016\/j.jdermsci.2018.08.010","journal-title":"J Dermatol Sci"},{"key":"864_CR42","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1182\/blood-2013-07-514992","volume":"123","author":"AS Savchenko","year":"2014","unstructured":"Savchenko AS, Borissoff JI, Martinod K, De Meyer SF, Gallant M, Erpenbeck L, Brill A, Wang Y, Wagner DD (2014) VWF-mediated leukocyte recruitment with chromatin decondensation by PAD4 increases myocardial ischemia\/reperfusion injury in mice. Blood 123:141\u2013148. https:\/\/doi.org\/10.1182\/blood-2013-07-514992","journal-title":"Blood"},{"key":"864_CR43","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1093\/eurheartj\/ehv007","volume":"36","author":"DA Stakos","year":"2015","unstructured":"Stakos DA, Kambas K, Konstantinidis T, Mitroulis I, Apostolidou E, Arelaki S, Tsironidou V, Giatromanolaki A, Skendros P, Konstantinides S, Ritis K (2015) Expression of functional tissue factor by neutrophil extracellular traps in culprit artery of acute myocardial infarction. Eur Heart J 36:1405\u20131414. https:\/\/doi.org\/10.1093\/eurheartj\/ehv007","journal-title":"Eur Heart J"},{"key":"864_CR44","doi-asserted-by":"publisher","first-page":"2497","DOI":"10.1056\/NEJMoa1912388","volume":"381","author":"JC Tardif","year":"2019","unstructured":"Tardif JC, Kouz S, Waters DD, Bertrand OF, Diaz R, Maggioni AP, Pinto FJ, Ibrahim R, Gamra H, Kiwan GS, Berry C, L\u00f3pez-Send\u00f3n J, Ostadal P, Koenig W, Angoulvant D, Gr\u00e9goire JC, Lavoie MA, Dub\u00e9 MP, Rhainds D, Provencher M, Blondeau L, Orfanos A, L\u2019Allier PL, Guertin MC, Roubille F (2019) Efficacy and safety of low-dose colchicine after myocardial infarction. N Engl J Med 381:2497\u20132505. https:\/\/doi.org\/10.1056\/NEJMoa1912388","journal-title":"N Engl J Med"},{"key":"864_CR45","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1007\/s12026-017-8905-3","volume":"65","author":"C Thalin","year":"2017","unstructured":"Thalin C, Daleskog M, Goransson SP, Schatzberg D, Lasselin J, Laska AC, Kallner A, Helleday T, Wallen H, Demers M (2017) Validation of an enzyme-linked immunosorbent assay for the quantification of citrullinated histone H3 as a marker for neutrophil extracellular traps in human plasma. Immunol Res 65:706\u2013712. https:\/\/doi.org\/10.1007\/s12026-017-8905-3","journal-title":"Immunol Res"},{"key":"864_CR46","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1111\/febs.12608","volume":"281","author":"M Ueki","year":"2014","unstructured":"Ueki M, Kimura-Kataoka K, Takeshita H, Fujihara J, Iida R, Sano R, Nakajima T, Kominato Y, Kawai Y, Yasuda T (2014) Evaluation of all non-synonymous single nucleotide polymorphisms (SNPs) in the genes encoding human deoxyribonuclease I and I-like 3 as a functional SNP potentially implicated in autoimmunity. FEBS J 281:376\u2013390. https:\/\/doi.org\/10.1111\/febs.12608","journal-title":"FEBS J"},{"key":"864_CR47","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/s00395-015-0472-y","volume":"110","author":"B Vogel","year":"2015","unstructured":"Vogel B, Shinagawa H, Hofmann U, Ertl G, Frantz S (2015) Acute DNase1 treatment improves left ventricular remodeling after myocardial infarction by disruption of free chromatin. Basic Res Cardiol 110:15. https:\/\/doi.org\/10.1007\/s00395-015-0472-y","journal-title":"Basic Res Cardiol"},{"key":"864_CR48","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1111\/nyas.12445","volume":"1319","author":"J Wang","year":"2014","unstructured":"Wang J, Arase H (2014) Regulation of immune responses by neutrophils. Ann N Y Acad Sci 1319:66\u201381. https:\/\/doi.org\/10.1111\/nyas.12445","journal-title":"Ann N Y Acad Sci"},{"key":"864_CR49","doi-asserted-by":"publisher","first-page":"9294","DOI":"10.1038\/s41598-018-27639-z","volume":"8","author":"X Wang","year":"2018","unstructured":"Wang X, Yang D, Liu J, Fan X, Ma A, Liu P (2018) Prognostic value of culprit artery double-stranded DNA in ST-segment elevated myocardial infarction. Sci Rep 8:9294. https:\/\/doi.org\/10.1038\/s41598-018-27639-z","journal-title":"Sci Rep"},{"key":"864_CR50","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1126\/science.aaa8064","volume":"349","author":"A Warnatsch","year":"2015","unstructured":"Warnatsch A, Ioannou M, Wang Q, Papayannopoulos V (2015) Inflammation. Neutrophil extracellular traps license macrophages for cytokine production in atherosclerosis. Science 349:316\u2013320. https:\/\/doi.org\/10.1126\/science.aaa8064","journal-title":"Science"},{"key":"864_CR51","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1016\/j.biocel.2010.04.012","volume":"42","author":"T Yasuda","year":"2010","unstructured":"Yasuda T, Ueki M, Takeshita H, Fujihara J, Kimura-Kataoka K, Iida R, Tsubota E, Soejima M, Koda Y, Kato H, Panduro A (2010) A biochemical and genetic study on all non-synonymous single nucleotide polymorphisms of the gene encoding human deoxyribonuclease I potentially relevant to autoimmunity. Int J Biochem Cell Biol 42:1216\u20131225. https:\/\/doi.org\/10.1016\/j.biocel.2010.04.012","journal-title":"Int J Biochem Cell Biol"},{"key":"864_CR52","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/91070","volume":"28","author":"K Yasutomo","year":"2001","unstructured":"Yasutomo K, Horiuchi T, Kagami S, Tsukamoto H, Hashimura C, Urushihara M, Kuroda Y (2001) Mutation of DNASE1 in people with systemic lupus erythematosus. Nat Genet 28:313\u2013314. https:\/\/doi.org\/10.1038\/91070","journal-title":"Nat Genet"},{"key":"864_CR53","doi-asserted-by":"publisher","first-page":"D754","DOI":"10.1093\/nar\/gkx1098","volume":"46","author":"DR Zerbino","year":"2018","unstructured":"Zerbino DR, Achuthan P, Akanni W, Amode MR, Barrell D, Bhai J, Billis K, Cummins C, Gall A, Giron CG, Gil L, Gordon L, Haggerty L, Haskell E, Hourlier T, Izuogu OG, Janacek SH, Juettemann T, To JK, Laird MR, Lavidas I, Liu Z, Loveland JE, Maurel T, McLaren W, Moore B, Mudge J, Murphy DN, Newman V, Nuhn M, Ogeh D, Ong CK, Parker A, Patricio M, Riat HS, Schuilenburg H, Sheppard D, Sparrow H, Taylor K, Thormann A, Vullo A, Walts B, Zadissa A, Frankish A, Hunt SE, Kostadima M, Langridge N, Martin FJ, Muffato M, Perry E, Ruffier M, Staines DM, Trevanion SJ, Aken BL, Cunningham F, Yates A, Flicek P (2018) Ensembl 2018. Nucleic Acids Res 46:D754-d761. https:\/\/doi.org\/10.1093\/nar\/gkx1098","journal-title":"Nucleic Acids Res"}],"container-title":["Basic Research in Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00395-021-00864-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00395-021-00864-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00395-021-00864-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T18:07:42Z","timestamp":1642615662000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00395-021-00864-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,23]]},"references-count":53,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["864"],"URL":"https:\/\/doi.org\/10.1007\/s00395-021-00864-w","relation":{},"ISSN":["0300-8428","1435-1803"],"issn-type":[{"value":"0300-8428","type":"print"},{"value":"1435-1803","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,23]]},"assertion":[{"value":"7 September 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 March 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 April 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"None.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"This study was approved by the Ethics Committee of the Medical University of Vienna, Austria (approval reference numbers 303\/2005, 1947\/2014). The \u201cKooperative Gesundheitsforschung in der Region Augsburg\u201d (KORA) study [] was approved by the Ethics Committee of the Bavarian Medical Association, Germany. All procedures were performed according to ethical standards of the Declaration of Helsinki 2013.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"All participants gave written informed consent.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"All authors gave consent to publish the manuscript.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"29"}}