miR-499 in Platelet-Derived Extracellular Vesicles Augments Inflammatory Cell Generation and Cardiac Remodeling After Myocardial Infarction
Authors' conclusion
Our study suggests that pEVs generated after MI induce HSPC proliferation and inflammatory cell generation.
Study context
- Population
- Mice with myocardial infarction (MI) (coronary artery ligation) or hindlimb ischemia, and patients with MI
Main finding
As reported in the abstract
- Patients and mice with MI and mice with hindlimb ischemia have increased circulating platelet-derived extracellular vesicles (pEVs), which augment bone marrow HSPC number and proliferation, leading to inflammatory myeloid cell generation and disease progression
- S100A8/9, an alarmin produced by cardiomyocytes after MI, induced pEV secretion
- Inhibition of platelet activation and exocytosis, and of HSPC endocytosis, markedly lessened pEV production, HSPC proliferation and myeloid cell generation
- pEVs after MI had elevated miR-499 and miR-184, enriched in reticulated platelets; their overexpression in mouse and human hematopoietic stem and progenitor cells (HSPCs) enhanced hematopoiesis and myelopoiesis
- miR-499-deficient pEVs were inefficient in stimulating emergency myelopoiesis and inducing cardiac remodeling after MI
- miR-499 bound the 3' region of lactoferrin/lactotransferrin in HSPC, downregulating it, promoting myelopoiesis and inflammation
Original publication
miR-499 in Platelet-Derived Extracellular Vesicles Augments Inflammatory Cell Generation and Cardiac Remodeling After Myocardial Infarction. Circulation. Published 10 November 2025. doi:10.
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