{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T14:28:20Z","timestamp":1780496900918,"version":"3.54.1"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"17","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences","award":["2021-I2M-1-008"],"award-info":[{"award-number":["2021-I2M-1-008"]}]},{"name":"Special Research Fund for Central Universities"},{"DOI":"10.13039\/501100011176","name":"Peking Union Medical College","doi-asserted-by":"publisher","award":["3332023021"],"award-info":[{"award-number":["3332023021"]}],"id":[{"id":"10.13039\/501100011176","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Despite advancements in primary percutaneous coronary intervention (PCI), cardiac dysfunction remains a challenge in patients with ST-segment elevation myocardial infarction (STEMI). Although thymosin beta 4 has shown cardioprotective effects in preclinical MI models, its impact on chronic cardiac functional recovery post ischemia\/reperfusion (I\/R), especially in STEMI, warrants further investigation. This study aims to explore the therapeutic potential of recombinant human thymosin beta 4 (rhTB4) in both murine models subjected to I\/R and in subjects with STEMI post-PCI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>In C57BL\/6J mice, 7-day rhTB4 treatment prevented cardiac dysfunction and fibrosis 28 days post-I\/R surgery and significantly reduced plasma NT-proBNP levels at both 1 day and 28 days post-I\/R. Similarly, in a permanent ligation model, rhTB4 improved cardiac function and reduced infarct size at 8 weeks post-MI. RNA-seq analysis of I\/R heart tissues revealed that rhTB4 modulated the ErbB signaling pathway. In vitro hypoxia\/reoxygenation (H\/R) models (HL-1, neonatal mouse cardiomyocytes, H9C2) demonstrated that rhTB4 activated the ErbB2\/Raf1 signaling pathway, attenuated cardiomyocyte apoptosis and suppressed pro-apoptotic protein Bad expression. The cardioprotective effects of rhTB4 on cardiac function and adverse cardiac remodeling in I\/R mice were abolished by ErbB2 inhibition. In a randomized, placebo-controlled, double-blind trial involving 96 STEMI patients, the infarcted areas were significantly reduced in the rhTB4 group, which received the first dose of rhTB4 within 8\u2005h after PCI (n = 43), as compared to the placebo group at the 90-day follow-up. However, the overall differences in infarcted areas were not significantly between the rhTB4 group and the placebo group (n = 96).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings underscore the crucial role of rhTB4 in mitigating cardiac dysfunction in an ErbB2-dependent manner. The clinical relevance of rhTB4 is demonstrated through a randomized controlled trial, emphasizing its translational potential. Further rigorous randomized studies are needed to assess the significance of early rhTB4 use post-myocardial infarction reperfusion.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvaf223","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T12:59:37Z","timestamp":1762865977000},"page":"2747-2758","source":"Crossref","is-referenced-by-count":2,"title":["Recombinant human thymosin beta 4 improves ischemic cardiac dysfunction in mice and patients with acute ST-segment elevation myocardial infarction after reperfusion"],"prefix":"10.1093","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5869-2033","authenticated-orcid":false,"given":"Yuze","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease, Cardiometabolic Medicine Center, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union 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