{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:11:47Z","timestamp":1790727107715,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AATS Foundation Cardiac Surgical Resident Investigator Award","award":["R01HL157215"],"award-info":[{"award-number":["R01HL157215"]}]},{"name":"AATS Foundation Cardiac Surgical Resident Investigator Award","award":["R01EY036243"],"award-info":[{"award-number":["R01EY036243"]}]},{"name":"AATS Foundation Cardiac Surgical Resident Investigator Award","award":["R01AG072430"],"award-info":[{"award-number":["R01AG072430"]}]},{"name":"AATS Foundation Cardiac Surgical Resident Investigator Award","award":["R01HL155116"],"award-info":[{"award-number":["R01HL155116"]}]},{"name":"NIH","award":["R01HL157215"],"award-info":[{"award-number":["R01HL157215"]}]},{"name":"NIH","award":["R01EY036243"],"award-info":[{"award-number":["R01EY036243"]}]},{"name":"NIH","award":["R01AG072430"],"award-info":[{"award-number":["R01AG072430"]}]},{"name":"NIH","award":["R01HL155116"],"award-info":[{"award-number":["R01HL155116"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Background: Excessive formation of neutrophil extracellular traps (NETs) leads to NETosis, accompanied by the release of citrullinated histone H3 (CitH3), a key mediator of septic inflammation. However, the role of CitH3 in sterile inflammation, such as acute myocardial infarction (MI) and post-MI heart failure, remains incompletely understood. Methods and Results: We investigated the role of CitH3, a byproduct of NETosis, in myocardial ischemia\/reperfusion (I\/R) injury using a murine MI model. C57BL\/6J mice were subjected to left coronary artery (LCA) occlusion followed by reperfusion and treated with either a humanized anti-CitH3 monoclonal antibody (hCitH3-mAb) or control human IgG. In mice undergoing 40 min of LCA occlusion and 24 h of reperfusion, hCitH3-mAb administered 10 min before reperfusion significantly reduced infarct size by 36% compared to control (p &lt; 0.05). Plasma levels of CitH3, IL-1\u03b2, and interferon-\u03b2 were significantly elevated following MI but were attenuated by hCitH3-mAb. In addition, plasma and cardiac tissue from treated mice showed significantly lower levels of citrate synthase, a marker of mitochondrial injury, suggesting that hCitH3-mAb preserved mitochondrial integrity after MI. In mice undergoing 50 min of LCA occlusion and 21 days of reperfusion, longitudinal echocardiography revealed preservation of left ventricular ejection fraction (LVEF) in hCitH3-mAb-treated mice, with significant improvement observed on days 7, 14, and 21 post-MI (p &lt; 0.05 vs. control). hCitH3-mAb also mitigated myocardial fibrosis and preserved tissue architecture. Conclusions: These findings demonstrated CitH3 as a critical mediator of myocardial injury and adverse remodeling following acute MI. Neutralization of CitH3 via hCitH3-mAb attenuates I\/R injury and preserves cardiac function by mitigating inflammation and protecting mitochondrial integrity. Targeting CitH3 represents a promising therapeutic strategy to prevent heart failure following MI.<\/jats:p>","DOI":"10.3390\/biom15081196","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T07:50:46Z","timestamp":1755676246000},"page":"1196","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Humanized Monoclonal Antibody Against Citrullinated Histone H3 Attenuates Myocardial Injury and Prevents Heart Failure in Rodent Models"],"prefix":"10.3390","volume":"15","author":[{"given":"Matthew","family":"Weber","sequence":"first","affiliation":[{"name":"Department of Surgery, University of Virginia, Charlottesville, VA 22903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Virginia, Charlottesville, VA 22903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Virginia, Charlottesville, VA 22903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heejae","family":"Chun","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Virginia, Charlottesville, VA 22903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Virginia, Charlottesville, VA 22903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6193-9826","authenticated-orcid":false,"given":"Ki Ho","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Virginia, Charlottesville, VA 22903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanxi","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Virginia, Charlottesville, VA 22903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Michigan Health System, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjie","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Virginia, Charlottesville, VA 22903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zequan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Virginia, Charlottesville, VA 22903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e347","DOI":"10.1161\/CIR.0000000000001209","article-title":"2024 Heart Disease and Stroke Statistics: A Report of US and Global Data from the American Heart Association","volume":"149","author":"Martin","year":"2024","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Mulay, S.R., and Anders, H.J. 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