Cardiovascular drugs and therapy · 2026
High Mobility Group Protein B1 Mediates the Role of the Neutrophil Extracellular Traps in the Progression of Acute Myocardial Infarction.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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He Jing, Wang Landi, Xu Chen, Liu Jingyi, Wang Yuchao, Han Jing, Zhang Jianhong, Li Dayong, Li Huanming, Liu Yong, Liu Xuan
Аннотация
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.
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.