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Background <p>Neutrophil extracellular traps (NETs) play a crucial role in the pathogenesis of acute myocardial infarction (AMI), but the role of high-mobility group box 1 (HMGB1), a key target of the cell migration family, remains unclear.</p> Methods <p>This study investigated the HMGB1-CXCR4/CXCL12 -NETs pathway in ST-segment elevation myocardial infarction (STEMI) patients and a murine myocardial infarction (MI) model, with a focus on mechanisms associated with injury and aging.</p> Results <p>Peripheral blood analysis in 29 STEMI patients revealed elevated HMGB1 and myeloperoxidase (MPO) levels compared to controls. In C57BL/6J mice subjected to permanent left anterior descending (LAD) ligation, the CXCR4/CXCL12 axis was significantly upregulated in infarcted hearts, correlating with impaired ventricular function. Deoxyribonuclease (DNase) I or glycyrrhizic acid (a HMGB1 inhibitor) attenuated NETs formation and CXCR4/CXCL12 activation. Histological, echocardiographic, and transcriptomic analyses revealed that HMGB1 promotes NETs formation, exacerbating cardiac inflammation and fibrosis. Flow cytometry of murine blood demonstrated altered CD62L/CD11b expression, suggesting age-like immunophenotypic shifts in post-MI inflammation.</p> Conclusion <p>These findings delineate a pivotal HMGB1-CXCR4/CXCL12-NETs axis in AMI pathology, driving cardiac injury through inflammation and fibrosis, with implications for cellular aging/senescence. Targeting this pathway presents a promising therapeutic strategy for mitigating ischemia-related damage.</p>

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High Mobility Group Protein B1 Mediates the Role of the Neutrophil Extracellular Traps in the Progression of Acute Myocardial Infarction

  • 期刊论文

  • 发表日期：

    2026年1月24日

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  • Jing He,
  • Landi Wang,
  • Chen Xu,
  • Jingyi Liu,
  • Yuchao Wang,
  • Jing Han,
  • Jianhong Zhang,
  • Dayong Li,
  • Huanming Li,
  • Yong Liu,
  • Xuan Liu

摘要

Background

Neutrophil extracellular traps (NETs) play a crucial role in the pathogenesis of acute myocardial infarction (AMI), but the role of high-mobility group box 1 (HMGB1), a key target of the cell migration family, remains unclear.

Methods

This study investigated the HMGB1-CXCR4/CXCL12 -NETs pathway in ST-segment elevation myocardial infarction (STEMI) patients and a murine myocardial infarction (MI) model, with a focus on mechanisms associated with injury and aging.

Results

Peripheral blood analysis in 29 STEMI patients revealed elevated HMGB1 and myeloperoxidase (MPO) levels compared to controls. In C57BL/6J mice subjected to permanent left anterior descending (LAD) ligation, the CXCR4/CXCL12 axis was significantly upregulated in infarcted hearts, correlating with impaired ventricular function. Deoxyribonuclease (DNase) I or glycyrrhizic acid (a HMGB1 inhibitor) attenuated NETs formation and CXCR4/CXCL12 activation. Histological, echocardiographic, and transcriptomic analyses revealed that HMGB1 promotes NETs formation, exacerbating cardiac inflammation and fibrosis. Flow cytometry of murine blood demonstrated altered CD62L/CD11b expression, suggesting age-like immunophenotypic shifts in post-MI inflammation.

Conclusion

These findings delineate a pivotal HMGB1-CXCR4/CXCL12-NETs axis in AMI pathology, driving cardiac injury through inflammation and fibrosis, with implications for cellular aging/senescence. Targeting this pathway presents a promising therapeutic strategy for mitigating ischemia-related damage.