{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T02:18:00Z","timestamp":1790907480340,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2025,9,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Myocardial ischemia\/reperfusion injury (MI\/R) remains a major challenge in cardiac transplantation, leading to early graft dysfunction or primary nonfunction, and eventually death. This study explores the role of annexin A4 (ANXA4), a calcium\u2010dependent phospholipid\u2010binding protein, in MI\/R pathogenesis and investigates its underlying mechanisms. In C57BL\/6J mice, ANXA4 expression was moderately increased following MI\/R (induced by 45\u2010min occlusion\/24 h reperfusion) (mRNA: sham vs. MI\/\n                    <jats:italic>R<\/jats:italic>\n                    \u2009=\u20091.00 vs. 2.42,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01; protein: 1.00 vs. 2.39,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). To assess its functional role, AAV9 particles (1\u2009\u00d7\u200910\n                    <jats:sup>11<\/jats:sup>\n                    viral genomes per mouse) carrying ANXA4 encoding fragments were intravenously injected into mice 4\u2009weeks before the surgery. The forced elevation of ANXA4 reduced IR\u2010induced myocardial infarction from 41.22% to 18.23%, lowered the ventricular arrhythmias score from 10.83 to 6.00, and creatinine kinase\u2010myocardial band (CK\u2010MB) activity from 450 to 268\u2009U\/L. ANXA4 overexpression also inhibited cardiomyocyte apoptosis, inflammation, and oxidative stress. In\u00a0vitro, ANXA4 overexpression mediated by pcDNA3.1 vector protected HL\u20101 mouse cardiomyocytes against oxygen\u2013glucose deprivation\/reoxygenation (OGD\/R)\u2010induced cell damage. Further high\u2010throughput transcriptomics illustrated that ANXA4 upregulation significantly suppressed the expression of the receptor for advanced glycosylation end products (RAGE; Log2 Fold change\u2009=\u2009\u22123.19,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Mechanistically, ANXA4 repressed the transcription of RAGE by dampening the nuclear translocation of NF\u03baB p50. Collectively, this study demonstrates that ANXA4 is upregulated in the mouse myocardium post MI\/R as a compensatory response, and its overexpression alleviates MI\/R\u2010 and OGD\/R\u2010induced cardiomyocyte injury by preventing NF\u03baB p50 from binding to and initiating transcription of RAGE.\n                  <\/jats:p>","DOI":"10.1096\/fj.202501598r","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T16:14:17Z","timestamp":1758125657000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>ANXA4<\/scp>\n                    Alleviates Cardiomyocyte Injury Associated With Ischemia\u2013Reperfusion by Interfering With\n                    <scp>NF\u03baB<\/scp>\n                    p50's Transcriptional Activation of\n                    <scp>RAGE<\/scp>"],"prefix":"10.1096","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4346-2335","authenticated-orcid":false,"given":"Zhihan","family":"Zhao","sequence":"first","affiliation":[{"name":"Heart Center of Henan Provincial People's Hospital, Central China Fuwai Hospital Central China Fuwai Hospital of Zhengzhou University  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghui","family":"Zhao","sequence":"additional","affiliation":[{"name":"Heart Center of Henan Provincial People's Hospital, Central China Fuwai Hospital Central China Fuwai Hospital of Zhengzhou University  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobiao","family":"Zang","sequence":"additional","affiliation":[{"name":"Heart Center of Henan Provincial People's Hospital, Central China Fuwai Hospital Central China Fuwai Hospital of Zhengzhou University  Zhengzhou Henan 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