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Publication : High glucose macrophage exosomes enhance atherosclerosis by driving cellular proliferation & hematopoiesis.

First Author  Bouchareychas L Year  2021
Journal  iScience Volume  24
Issue  8 Pages  102847
PubMed ID  34381972 Mgi Jnum  J:350641
Mgi Id  MGI:6828563 Doi  10.1016/j.isci.2021.102847
Citation  Bouchareychas L, et al. (2021) High glucose macrophage exosomes enhance atherosclerosis by driving cellular proliferation & hematopoiesis. iScience 24(8):102847
abstractText  We 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 and Abca1 control. Together, our findings show that EVs serve to communicate detrimental properties of hyperglycemia to accelerate atherosclerosis in diabetes.
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