M1 macrophage-derived migrasomes significantly reduced left ventricular ejection fraction and increased left ventricular end-diastolic volume compared to the M0-migrasomes and MI groups, indicating exacerbated myocardial injury post-MI.
M1 macrophage-derived migrasomes exacerbate post-myocardial infarction injury by promoting cardiomyocyte apoptosis through GBP5-mediated NF-κB pathway activation, identifying a novel therapeutic target.
Effect estimate: null (95% CI null)
p-value: p=null
Myocardial infarction (MI) is a complex pathological process characterized by vascular injury, myocardial necrosis, and dynamic immune interactions. Migrasomes are recently identified organelles generated during cell migration, serving as key mediators of intercellular communication. However, the contribution of migrasomes to immune-mediated myocardial injury remains largely unexplored. This study demonstrated an increase in migrasome production following MI. Migrasomes can be produced by macrophages, and M1 macrophage-derived migrasomes (M1-Migs) were particularly found to exacerbate myocardial tissue injury. Quantitative proteomic sequencing demonstrated increased levels of guanylate binding protein 5 (GBP5) within M1-Migs. Viral knockdown experiments demonstrated that M1-Migs mediate their deleterious effects predominantly via GBP5. Pathway enrichment analysis further indicated that GBP5 activates nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, thereby promoting myocardial cell apoptosis. Analysis of clinical samples has also demonstrated a positive correlation between macrophage-derived migrasomes and MI. Notably, colchicine may mitigate post-infarction myocardial injury by suppressing migrasome production by M1 macrophages. Overall, these findings identify macrophage-derived migrasomes as key amplifiers of myocardial injury, providing potential therapeutic targets for MI and may provide additional evidence for the clinical application of colchicine.
Zhang et al. (2026) studied Post-myocardial infarction injury. M1 macrophage-derived migrasomes vs. M0 macrophage-derived migrasomes and myocardial infarction (MI) group was evaluated on Left ventricular ejection fraction (LVEF), fractional shortening (LVFS), left ventricular end-diastolic volume (LVEDV), infarct area, cardiomyocyte viability (null, 95% CI null, p=null). M1 macrophage-derived migrasomes significantly reduced left ventricular ejection fraction and increased left ventricular end-diastolic volume compared to the M0-migrasomes and MI groups, indicating exacerbated myocardial injury post-MI.