{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T08:31:08Z","timestamp":1775809868581,"version":"3.50.1"},"reference-count":51,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T00:00:00Z","timestamp":1731974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Stiftung KinderHerz Deutschland gGmbH, Essen, Germany","award":["2511-3-19-020"],"award-info":[{"award-number":["2511-3-19-020"]}]},{"name":"Stiftung KinderHerz Deutschland gGmbH, Essen, Germany","award":["F\/37\/20"],"award-info":[{"award-number":["F\/37\/20"]}]},{"DOI":"10.13039\/501100005970","name":"Deutsche Stiftung f\u00fcr Herzforschung","doi-asserted-by":"publisher","award":["2511-3-19-020"],"award-info":[{"award-number":["2511-3-19-020"]}],"id":[{"id":"10.13039\/501100005970","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005970","name":"Deutsche Stiftung f\u00fcr Herzforschung","doi-asserted-by":"publisher","award":["F\/37\/20"],"award-info":[{"award-number":["F\/37\/20"]}],"id":[{"id":"10.13039\/501100005970","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Congenital heart defects (CHDs) are one of the most common congenital malformations and often require heart surgery with cardiopulmonary bypass (CPB). Children undergoing cardiac surgery with CPB are especially at greater risk of post-operative complications due to a systemic inflammatory response caused by innate inflammatory mediators. However, the pathophysiological response is not fully understood and warrants further investigation. Therefore, we investigated the inflammatory response in macrophages initiated by peri-operative serum samples obtained from patients with CHD undergoing CPB cardiac surgery. Human differentiated THP-1 macrophages were pretreated with Stattic, a STAT3 (Tyr705) inhibitor, before stimulation with serum samples. STAT3 and NF-\u03baB activation were investigated via a Western blot, IL-1\u03b2, TNF\u03b1, IL-10, mediators for vascular permeability (VEGF-A, ICAM), and SOCS3 gene expressions via RT-qPCR. CPB induced an inflammatory response in macrophages via the activation of the STAT3 but not NF-\u03baB signaling pathway. Longer duration on the CPB correlated with increased cytokine, VEGF, and ICAM expressions, relative to individual pre-operation levels. Patients that did not require CPB showed no significant immune response. Pretreatment with Stattic significantly attenuated all inflammatory mediators investigated except for TNF\u03b1 in the macrophages. CPB induces an increased expression of cytokines and mediators of vascular permeability via the activation of STAT3 by IL-6 and IL-8 in the serum samples. Stattic attenuates all mediators investigated but promotes TNF\u03b1 expression.<\/jats:p>","DOI":"10.3390\/ijms252212398","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T04:53:05Z","timestamp":1731991985000},"page":"12398","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Prolonged Extracorporeal Circulation Leads to Inflammation and Higher Expression of Mediators of Vascular Permeability Through Activation of STAT3 Signaling Pathway in Macrophages"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8687-8313","authenticated-orcid":false,"given":"Jana","family":"Luecht","sequence":"first","affiliation":[{"name":"Department of Congenital Heart Disease\/Pediatric Cardiology, Deutsches Herzzentrum der Charit\u00e9, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5634-3940","authenticated-orcid":false,"given":"Camila","family":"Pauli","sequence":"additional","affiliation":[{"name":"Department of Developmental Pediatric Cardiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raphael","family":"Seiler","sequence":"additional","affiliation":[{"name":"Department of Congenital Heart Disease\/Pediatric Cardiology, Deutsches Herzzentrum der Charit\u00e9, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexa-Leona","family":"Herre","sequence":"additional","affiliation":[{"name":"Department of Developmental Pediatric Cardiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liliya","family":"Brankova","sequence":"additional","affiliation":[{"name":"Department of Developmental Pediatric Cardiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7881-1557","authenticated-orcid":false,"given":"Felix","family":"Berger","sequence":"additional","affiliation":[{"name":"Department of Congenital Heart Disease\/Pediatric Cardiology, Deutsches Herzzentrum der Charit\u00e9, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina R. L.","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Department of Developmental Pediatric Cardiology, Deutsches Herzzentrum der Charit\u00e9, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3470-9750","authenticated-orcid":false,"given":"Giang","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Developmental Pediatric Cardiology, Deutsches Herzzentrum der Charit\u00e9, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1007\/s00392-011-0355-7","article-title":"Frequency and spectrum of congenital heart defects among live births in Germany: A study of the Competence Network for Congenital Heart Defects","volume":"100","author":"Schwedler","year":"2011","journal-title":"Clin. Res. 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