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. |