{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:04:48Z","timestamp":1791857088017,"version":"4.3.4"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>Acute aortic dissection (AAD) is a life-threatening cardiovascular emergency. Both neutrophil granzyme and interleukin (IL)-33\/ST2 systems have proven to be effective diagnostic markers for AAD. This study aimed to investigate the relationship between plasma IL-33, soluble suppression of tumorigenesis-2 (sST2), myeloperoxidase (MPO), and matrix metalloproteinase (MMP)-9 levels at admission and all-cause mortality in patients with AAD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 155 patients with AAD were enrolled from the Prospective Evaluation of Acute Chest Pain (PEACP) study. Plasma concentrations of IL-33, sST2, and MMP-9 were measured using an enzyme-linked immunosorbent assay, and MPO was detected using a chemiluminescence immunoassay. Aortic anatomical parameters were measured using CT radiography. The primary endpoint was all-cause mortality rate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The median age of the patients was 55 years, and 96 (61.9%) were diagnosed with type A-AAD. After adjusting for confounding factors, the highest tertiles of IL-33, sST2, MPO, and MMP-9 had hazard risks of 0.870 (95% CI: 0.412\u20131.836, <jats:italic>P<\/jats:italic> = 0.714), 3.769 (95% CI: 1.504\u20139.446, <jats:italic>P<\/jats:italic> = 0.005), 4.689 (95% CI: 1.985\u201311.076, <jats:italic>P<\/jats:italic> &amp;lt; 0.001), and 4.748 (95% CI: 1.763\u201312.784, <jats:italic>P<\/jats:italic> = 0.002), respectively, compared to the lowest tertile. Pearson\u2019s correlation analysis revealed a significant correlation between these markers (<jats:italic>P<\/jats:italic> &amp;lt; 0.001). Moreover, sST2, MPO, and MMP-9 levels had a significant positive correlation with aortic diameter and pseudolumen area (<jats:italic>P<\/jats:italic> &amp;lt; 0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The biomarkers sST2, MPO, and MMP-9 were independently associated with mortality in patients with AAD. The significant correlation between these biomarkers suggests a pathogenic role for the IL-33\/ST2\/neutrophil granzyme system in patients with AAD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2022.1084321","type":"journal-article","created":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T19:58:42Z","timestamp":1673035122000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Prognostic value of interleukin-33, sST2, myeloperoxidase, and matrix metalloproteinase-9 in acute aortic dissection"],"prefix":"10.3389","volume":"9","author":[{"given":"Yu","family":"Jia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongze","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenli","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanghui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1001\/jama.283.7.897","article-title":"The international registry of acute aortic dissection (IRAD): new insights into an old disease.","volume":"283","author":"Hagan","year":"2000","journal-title":"JAMA."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.115.003172","article-title":"False lumen status in patients with acute aortic dissection: a systematic review and meta-analysis.","volume":"5","author":"Li","year":"2016","journal-title":"J Am Heart Assoc."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1846","DOI":"10.1161\/CIRCULATIONAHA.117.031264","article-title":"Insights from the international registry of acute aortic dissection: a 20-year experience of collaborative clinical research.","volume":"137","author":"Evangelista","year":"2018","journal-title":"Circulation."},{"key":"B4","doi-asserted-by":"publisher","first-page":"368","DOI":"10.3978\/j.issn.2225-319X.2014.07.06","article-title":"Acute type B aortic dissection: insights from the international registry of acute aortic dissection.","volume":"3","author":"Patel","year":"2014","journal-title":"Ann Cardiothorac Surg."},{"key":"B5","first-page":"214","article-title":"Contemporary management of type B aortic dissection in the endovascular era.","volume":"28","author":"Bannazadeh","year":"2016","journal-title":"Surg Technol Int."},{"key":"B6","doi-asserted-by":"publisher","first-page":"I249","DOI":"10.1161\/CIRCULATIONAHA.104.525733","article-title":"Large area of the false lumen favors secondary dilatation of the aorta after acute type A aortic dissection.","volume":"112","author":"Immer","year":"2005","journal-title":"Circulation."},{"key":"B7","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1016\/j.jtcvs.2018.05.126","article-title":"Fate of uncomplicated acute type B aortic dissection and impact of concurrent aortic dilatation on remote aortic events.","volume":"157","author":"Shimamoto","year":"2019","journal-title":"J Thorac Cardiovasc Surg."},{"key":"B8","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1016\/j.jcmg.2013.10.015","article-title":"The role of imaging in aortic dissection and related syndromes.","volume":"7","author":"Baliga","year":"2014","journal-title":"JACC Cardiovasc Imaging."},{"key":"B9","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1161\/CIRCRESAHA.116.304918","article-title":"Adventitial CXCL1\/G-CSF expression in response to acute aortic dissection triggers local neutrophil recruitment and activation leading to aortic rupture.","volume":"116","author":"Anzai","year":"2015","journal-title":"Circ Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.21470\/1678-9741-2020-0144","article-title":"Predictive value of white blood cells, neutrophils, platelets, platelet to lymphocyte and neutrophil to lymphocyte ratios in patients with acute aortic dissection.","volume":"35","author":"Liu","year":"2020","journal-title":"Braz J Cardiovasc Surg."},{"key":"B11","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/nri3024","article-title":"Neutrophils in the activation and regulation of innate and adaptive immunity.","volume":"11","author":"Mantovani","year":"2011","journal-title":"Nat Rev Immunol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1024\/0301-1526\/a000390","article-title":"Differential expression of MMP-2, MMP-9 and TIMP proteins in thoracic aortic aneurysm\u2013comparison with and without bicuspid aortic valve: a meta-analysis.","volume":"43","author":"Rabkin","year":"2014","journal-title":"Vasa."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21207678","article-title":"The role of inflammation and myeloperoxidase-related oxidative stress in the pathogenesis of genetically triggered thoracic aortic aneurysms.","volume":"21","author":"Malecki","year":"2020","journal-title":"Int J Mol Sci."},{"key":"B14","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1161\/CIRCULATIONAHA.117.030469","article-title":"Magnitude of soluble ST2 as a novel biomarker for acute aortic dissection.","volume":"137","author":"Wang","year":"2018","journal-title":"Circulation."},{"key":"B15","doi-asserted-by":"publisher","first-page":"12189","DOI":"10.7150\/thno.48028","article-title":"IL-33\/ST2 induces neutrophil-dependent reactive oxygen species production and mediates gout pain.","volume":"10","author":"Yin","year":"2020","journal-title":"Theranostics."},{"key":"B16","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1016\/j.jtos.2020.06.006","article-title":"Epithelium-derived IL-33 activates mast cells to initiate neutrophil recruitment following corneal injury.","volume":"18","author":"Elbasiony","year":"2020","journal-title":"Ocul Surf."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1878","DOI":"10.1182\/blood.2021013474","article-title":"Intestinal IL-33 promotes platelet activity for neutrophil recruitment during acute inflammation.","volume":"139","author":"Chen","year":"2022","journal-title":"Blood."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.09.010","article-title":"IL-33 exacerbates liver sterile inflammation by amplifying neutrophil extracellular trap formation.","author":"Yazdani","year":"2017","journal-title":"J Hepatol."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106256","article-title":"Interleukin-33 facilitates cutaneous defense against Staphylococcus aureus by promoting the development of neutrophil extracellular trap.","volume":"81","author":"Wang","year":"2020","journal-title":"Int Immunopharmacol."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-020-0267-2","article-title":"IL-33-induced neutrophil extracellular traps degrade fibronectin in a murine model of bronchopulmonary dysplasia.","volume":"6","author":"Jin","year":"2020","journal-title":"Cell Death Discov."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1595","DOI":"10.1056\/NEJMoa035003","article-title":"Prognostic value of myeloperoxidase in patients with chest pain.","volume":"349","author":"Brennan","year":"2003","journal-title":"N Engl J Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"307","DOI":"10.2459\/01.JCM.0000223251.26988.c5","article-title":"Plasma levels of metalloproteinases-9 and \u20132 in the acute and subacute phases of type A and type B aortic dissection.","volume":"7","author":"Sangiorgi","year":"2006","journal-title":"J Cardiovasc Med (Hagerstown)."},{"key":"B23","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/s0741-5214(99)70363-0","article-title":"Increased plasma levels of metalloproteinase-9 are associated with abdominal aortic aneurysms.","volume":"29","author":"McMillan","year":"1999","journal-title":"J Vasc Surg."},{"key":"B24","doi-asserted-by":"publisher","first-page":"I288","DOI":"10.1161\/hc37t1.094596","article-title":"Plasma levels of metalloproteinases-3 and \u20139 as markers of successful abdominal aortic aneurysm exclusion after endovascular graft treatment.","volume":"104","author":"Sangiorgi","year":"2001","journal-title":"Circulation."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1186\/s12872-018-0958-2","article-title":"Serum levels of matrix metalloproteinase 9 and toll-like receptor 4 in acute aortic dissection: a case-control study.","volume":"18","author":"Li","year":"2018","journal-title":"BMC Cardiovasc Disord."},{"key":"B26","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.cca.2019.10.029","article-title":"sST2 as a value-added biomarker in heart failure.","volume":"501","author":"Lotierzo","year":"2020","journal-title":"Clin Chim Acta."},{"key":"B27","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1042\/CS20160196","article-title":"Advances in heart failure: a review of biomarkers, emerging pharmacological therapies, durable mechanical support and telemonitoring.","volume":"131","author":"Moayedi","year":"2017","journal-title":"Clin Sci (Lond)."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0095055","article-title":"Soluble ST2 and interleukin-33 levels in coronary artery disease: relation to disease activity and adverse outcome.","volume":"9","author":"Demyanets","year":"2014","journal-title":"PLoS One."},{"key":"B29","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.cyto.2017.09.017","article-title":"Predictive value of low interleukin-33 in critically ill patients.","volume":"103","author":"Krychtiuk","year":"2018","journal-title":"Cytokine."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11010056","article-title":"Soluble ST2 and all-cause mortality in patients with chronic obstructive pulmonary disease-A 10-year cohort study.","volume":"11","author":"Urban","year":"2021","journal-title":"J Clin Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.1016\/j.jhep.2019.12.017","article-title":"IL-33\/ST2 pathway regulates neutrophil migration and predicts outcome in patients with severe alcoholic hepatitis.","volume":"72","author":"Artru","year":"2020","journal-title":"J Hepatol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1093\/icvts\/ivx286","article-title":"Impact of initial aortic diameter and false-lumen area ratio on type B aortic dissection prognosis.","volume":"26","author":"Matsushita","year":"2018","journal-title":"Interact Cardiovasc Thorac Surg."},{"key":"B33","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1583\/14-4671MR.1","article-title":"Large false lumen area is a predictor of failed false lumen volume reduction after stent-graft repair in type B aortic dissection.","volume":"21","author":"Kim","year":"2014","journal-title":"J Endovasc Ther."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1093\/cvr\/cvy166","article-title":"Conflicting vascular and metabolic impact of the IL-33\/sST2 axis.","volume":"114","author":"Altara","year":"2018","journal-title":"Cardiovasc Res."}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2022.1084321\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T20:02:59Z","timestamp":1673035379000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2022.1084321\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,6]]},"references-count":34,"alternative-id":["10.3389\/fcvm.2022.1084321"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2022.1084321","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,6]]},"article-number":"1084321"}}