2. Academic Validation
  3. High Mobility Group Protein B1 Mediates the Role of the Neutrophil Extracellular Traps in the Progression of Acute Myocardial Infarction

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

  • Cardiovasc Drugs Ther. 2026 Jan 24. doi: 10.1007/s10557-026-07836-z.
Jing He # 1,  Landi Wang # 2,  Chen Xu # 3,  Jingyi Liu 2,  Yuchao Wang 4,  Jing Han 2,  Jianhong Zhang 5,  Dayong Li 6,  Huanming Li 7,  Yong Liu 8,  Xuan Liu 9
Affiliations

Affiliations

  • 1 Department of Cardiology, Tianjin Fourth Central Hospital, No.3, Zhongshan Road, Hebei District, Tianjin, 300140, China.
  • 2 School of Medicine, Tianjin University, Tianjin, China.
  • 3 Department of Clinical Laboratory, Tianjin Fourth Central Hospital, Tianjin, China.
  • 4 Graduate School of Tianjin Medical University, Tianjin, China.
  • 5 Pharmacy Department, Tianjin Fourth Central Hospital, No.3, Zhongshan Road, Hebei District, Tianjin, China.
  • 6 General surgery department, NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Tianjin Institute of Endocrinology, Chu Hsien-I Memorial Hospital, Tianjin Medical University, Tianjin, China.
  • 7 Department of Cardiology, Tianjin Fourth Central Hospital, No.3, Zhongshan Road, Hebei District, Tianjin, 300140, China. [email protected].
  • 8 Department of Cardiology, Tianjin Fourth Central Hospital, No.3, Zhongshan Road, Hebei District, Tianjin, 300140, China. [email protected].
  • 9 Pharmacy Department, Tianjin Fourth Central Hospital, No.3, Zhongshan Road, Hebei District, Tianjin, China. [email protected].
  • # Contributed equally.
PMID: 41579229 DOI: 10.1007/s10557-026-07836-z
Abstract

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.

Keywords

Acute myocardial infarction; High-mobility group box 1; Neutrophil extracellular traps; “aged” neutrophils.

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