Neutrophil N1 polarization induced by cardiomyocyte-derived extracellular vesicle miR-9-5p aggravates myocardial ischemia/reperfusion injury

Autor: Yeshen Zhang, Xinzhong Li, Yining Dai, Yuan Han, Xiaomin Wei, Guoquan Wei, Weikun Chen, Siyu Kong, Yu He, Haobin Liu, Ning Ma, Jianping Bin, Ning Tan, Pengcheng He, Yuanhui Liu
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Journal of Nanobiotechnology, Vol 22, Iss 1, Pp 1-25 (2024)
Druh dokumentu: article
ISSN: 1477-3155
DOI: 10.1186/s12951-024-02902-w
Popis: Abstract Neutrophil polarization contributes to inflammation and its resolution, but the role of neutrophil polarization in myocardial ischemia/reperfusion (I/R) injury remains unknown. Cardiomyocytes (CMs) participate in cardiac inflammation by secreting extracellular vesicles (EVs). Therefore, we investigated the role of neutrophil polarization in myocardial I/R injury and the mechanism by which CM-derived EVs regulated neutrophil polarization. In the present study, our data showed that N1 neutrophil polarization enlarged cardiac infarct size and exacerbated cardiac dysfunction at the early stage of myocardial I/R. Further, CM-EV-derived miR-9-5p was identified as a mediator inducing neutrophils to the N1 phenotype. Mechanistically, miR-9-5p directly suppressed SOCS5 and SIRT1 expression, resulting in activating JAK2/STAT3 and NF-κB signaling pathways in neutrophils. Importantly, we confirmed that serum EV-derived miR-9-5p levels were independently associated with cardiovascular mortality in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention. These findings suggest neutrophil polarization is a promising therapeutic target against myocardial I/R-induced inflammation and injury, and serum EV-derived miR-9-5p is a promising prognostic biomarker for cardiovascular mortality in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention. Graphical Abstract
Databáze: Directory of Open Access Journals
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