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This study aimed to elucidate the underlying mechanisms responsible for this residual risk. Using Mendelian randomization analysis and retrospective cohort study, we established a causal relationship between MI and plaque progression, potentially mediated by neutrophils. In a murine atherosclerotic model, MI precipitated a marked expansion in plaque volume accompanied by reduced stability; these pathological changes are consistent with the hallmark features of rapid plaque progression, which may trigger recurrent ischemic events. Pharmacological inhibition and adoptive transfer experiments using\n                    <jats:italic toggle=\"yes\">\n                      Padi4\n                      <jats:sup>flox\/flox<\/jats:sup>\n                      Lyz2\n                      <jats:sup>Cre<\/jats:sup>\n                    <\/jats:italic>\n                    mice confirmed the pivotal role of neutrophils in MI-driven rapid plaque progression via neutrophil extracellular traps (NETs) formation. Further investigations revealed that NETs promote intraplaque hemorrhage by facilitating intraplaque angiogenesis and enhancing microvascular permeability, thereby exacerbating post-MI atherosclerotic inflammation. Mechanistically, bioinformatics analyses and in\u00a0vitro experiments identified the transcription factor ETS proto-oncogene 1 as a critical regulator of NETs-mediated angiogenesis and endothelial permeability through the activation of the vascular endothelial growth factor A\/vascular endothelial growth factor receptor 2 signaling pathway. In\u00a0vivo pharmacological inhibition of ETS proto-oncogene 1 with TK216 markedly attenuated the rapid plaque progression after MI. In summary, this study provides the first comprehensive evidence that neutrophils and NETs drive rapid plaque progression following MI by modulating intraplaque angiogenesis and hemorrhage. These findings offer novel insights into the mechanisms underlying post-MI ischemic event recurrence and highlight promising therapeutic targets for clinical prevention.\n                  <\/jats:p>","DOI":"10.34133\/research.1451","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:35:22Z","timestamp":1790685322000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":0,"title":["Neutrophil Extracellular Traps-Mediated Intraplaque Angiogenesis and Microvascular Permeability Promote Rapid Plaque Progression following Myocardial Infarction"],"prefix":"10.34133","volume":"9","author":[{"given":"Zhijun","family":"Lei","sequence":"first","affiliation":[{"name":"Department of Cardiology, Shanghai Tenth People\u2019s Hospital\r, Tongji University School of Medicine, Shanghai, China."},{"name":"Department of Cardiology, \rHuadong Hospital Affiliated to Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfei","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Tenth People\u2019s Hospital\r, Tongji University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Tenth People\u2019s Hospital\r, Tongji University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Tenth People\u2019s Hospital\r, Tongji University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Tenth People\u2019s Hospital\r, Tongji University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxi","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Tenth People\u2019s Hospital\r, Tongji University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yefei","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Tenth People\u2019s Hospital\r, Tongji University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Tenth People\u2019s Hospital\r, Tongji University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyu","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Tenth People\u2019s Hospital\r, Tongji University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixia","family":"Jian","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Xinhua Hospital, \rShanghai Jiaotong University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhui","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Tenth People\u2019s Hospital\r, Tongji University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Xinhua Hospital, \rShanghai Jiaotong University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2937-0024","authenticated-orcid":true,"given":"Wenhui","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Tenth People\u2019s Hospital\r, Tongji University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2026,10,19]]},"reference":[{"issue":"2","key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1093\/eurjhf\/hfq194","article-title":"Predictors and prognostic impact of recurrent myocardial infarction in patients with left ventricular dysfunction, heart failure, or both following a first myocardial infarction","volume":"13","author":"Thune JJ","year":"2011","unstructured":"Thune JJ, Signorovitch JE, Kober L, McMurray JJV, Swedberg K, Rouleau J, Maggioni A, Velazquez E, Califf R, Pfeffer MA, et al. 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