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

被引：34

作者：

Bouchareychas, Laura ^{[1
,2
]}

Duong, Phat ^{[2
]}

Phu, Tuan Anh ^{[2
]}

Alsop, Eric ^{[3
]}

Meechoovet, Bessie ^{[3
]}

Reiman, Rebecca ^{[3
]}

Ng, Martin ^{[2
]}

Yamamoto, Ryo ^{[4
,5
]}

Nakauchi, Hiromitsu ^{[4
,5
]}

Gasper, Warren J. ^{[1
,6
]}

Van Keuren-Jensen, Kendall ^{[3
]}

Raffai, Robert L. ^{[1
,2
,6
]}

机构：

[1] Univ Calif San Francisco, Dept Surg, Div Vasc & Endovasc Surg, San Francisco, CA 94143 USA

[2] Northern Calif Inst Res & Educ, San Francisco, CA 94121 USA

[3] Translat Genom Res Inst TGen, Neurogen, Phoenix, AZ 85004 USA

[4] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Sch Med, Lorry I Lokey Stem Cell Res Bldg,265 Campus Dr, Stanford, CA 94305 USA

[5] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA

[6] San Francisco VA Med Ctr, Dept Vet Affairs, Surg Serv 112G,4150 Clement St, San Francisco, CA 94121 USA

来源：

ISCIENCE | 2021年 / 24卷 / 08期

关键词：

EXTRACELLULAR VESICLES; EMERGING ROLES; STEM-CELLS; ACCUMULATION; MONOCYTOSIS; MICRORNAS; DISEASE; IMPAIRS; LESIONS; GROWTH;

D O I：

10.1016/j.isci.2021.102847

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：29

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