{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:06:03Z","timestamp":1791349563935,"version":"4.3.1"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T00:00:00Z","timestamp":1772841600000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101851"],"award-info":[{"award-number":["82101851"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Septic cardiomyopathy (SCM) is a common and life\u2010threatening complication of severe sepsis, with high mortality due to unclear underlying mechanisms. CXCL4, a key pro\u2010inflammatory factor, is implicated in various heart diseases, while ferroptosis (iron and lipid hydrogen peroxide\u2010dependent regulated cell death) plays a crucial role in SCM progression. However, the specific crosstalk between CXCL4, ferroptosis, and SCM remains unelucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>BALB\/c mice were randomly divided into six groups (Control, LPS, LPS + Sodium Cromoglycate (CS), LPS + Ferrostatin\u20101 (Fer\u20101), LPS + Pifithrin\u2010\u03b1 (PFT\u2010\u03b1), LPS + Niclosamide) to establish the SCM model via intraperitoneal LPS injection. In vivo experiments included histopathological examination (H&amp;E, toluidine blue staining), survival analysis, ELISA, Western blot, immunofluorescence, immunohistochemistry, TUNEL staining, and detection of myocardial markers (CK\u2010MB, AST, LDH) and oxidative stress indicators (SOD, MDA, iron content). In vitro, RAW264.7 macrophages were treated with CXCL4 alone or combined with inhibitors (Fer\u20101, PFT\u2010\u03b1, Niclosamide), followed by CCK\u20108 assay, ROS detection, qRT\u2010PCR, Western blot, and phagocytosis microbead assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In vivo, SCM mice exhibited significantly elevated CXCL4 levels in serum and heart tissue, accompanied by mast cell activation and degranulation. Inhibiting mast cell activation (with CS) reduced CXCL4 production, alleviated cardiac inflammation and ferroptosis (increased SLC7A11\/GPX4 expression, decreased 4\u2010HNE), and improved survival. TUNEL staining revealed predominant macrophage death in SCM hearts. In vitro, CXCL4 induced macrophage ferroptosis (downregulated SLC7A11\/GPX4) and impaired phagocytic function (reduced CD36\/MERTK expression), which was reversed by Fer\u20101. Mechanistically, CXCL4 activated STAT3 phosphorylation, regulating downstream P53; inhibiting STAT3 (Niclosamide) or P53 (PFT\u2010\u03b1) alleviated macrophage ferroptosis, restored phagocytosis, and mitigated cardiac injury in SCM mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Mast cell\u2010derived CXCL4 induces macrophage ferroptosis via the STAT3\/P53 signaling pathway, impairs macrophage phagocytic function, and exacerbates myocardial injury in SCM. Targeting mast cell activation, CXCL4 release, or the STAT3\/P53\u2010ferroptosis axis may serve as promising therapeutic strategies for SCM.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Clinical trial number:<\/jats:bold>\n                      Not applicable.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/iid3.70359","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T17:22:50Z","timestamp":1772990570000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Mast Cell\u2010Derived CXCL4: A Key Mediator of Ferroptosis and Cardiac Damage in Septic Cardiomyopathy"],"prefix":"10.1002","volume":"14","author":[{"given":"Jing","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine Jiangning Hospital Affiliated to Nanjing Medical University Nanjing China"},{"name":"Department of Laboratory 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