摘要：SummaryWe investigated whether extracellular vesicles (EVs) produced under hyperglycemic conditions could communicate signaling to drive atherosclerosis. We did so by treating Apoe−/−mice with exosomes produced by bone marrow-derived macrophages (BMDM) exposed to high glucose (BMDM–HG-exo) or control. Infusions of BMDM–HG-exo increased hematopoiesis, circulating myeloid cell numbers, and atherosclerotic lesions with an accumulation of macrophage foam and apoptotic cells. Transcriptome-wide analysis of cultured macrophages treated with BMDM–HG-exo or plasma EVs isolated from subjects with type II diabetes revealed a reduced inflammatory state and increased metabolic activity. Furthermore, BMDM–HG-exo induced cell proliferation and reprogrammed energy metabolism by increasing glycolytic activity. Lastly, profiling microRNA in BMDM–HG-exo and plasma EVs from diabetic subjects with advanced atherosclerosis converged on miR-486-5p as commonly enriched and recognized in dysregulated hematopoiesis andAbca1control. Together, our findings show that EVs serve to communicate detrimental properties of hyperglycemia to accelerate atherosclerosis in diabetes.Graphical abstractDisplay OmittedHighlights•Macrophages cultured in high glucose (HG) produce pro-atherogenic exosomes•HG exosomes drive glycolysis in recipient macrophages & monocytosis in Apoe–/–mice•HG macrophage exosomes & human diabetic PAD plasma EVs are rich in miR-486-5pEndocrine system physiology; Cell biology
