High glucose macrophage exosomes enhance atherosclerosis by driving cellular proliferation & hematopoiesis.
High glucose macrophage exosomes enhance atherosclerosis by driving cellular proliferation & hematopoiesis.
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高葡萄糖巨噬细胞外泌体通过驱动细胞增殖和造血来增强动脉粥样硬化。
DOI：
10.1016/j.isci.2021.102847
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发表时间：
2021-08-20
期刊：
影响因子：
5.8
通讯作者：
Raffai RL
中科院分区：
文献类型：
--
作者：
Bouchareychas L;Duong P;Phu TA;Alsop E;Meechoovet B;Reiman R;Ng M;Yamamoto R;Nakauchi H;Gasper WJ;Van Keuren-Jensen K;Raffai RL
我们研究了在高血糖条件下产生的细胞外囊泡（EV）是否可以传递信号以驱动动脉粥样硬化。我们通过用暴露于高葡萄糖（BMDM-HG-exo）或对照的骨髓源性巨噬细胞（BMDM）产生的外泌体治疗Apoe−/−小鼠来做到这一点。BMDM-HG-exo的输注增加了造血、循环髓样细胞数量和动脉粥样硬化病变，并伴有巨噬细胞泡沫和凋亡细胞的积累。用BMDM-HG-exo或从患有II型糖尿病的受试者分离的血浆EV处理的培养的巨噬细胞的全转录组分析揭示了炎症状态的降低和代谢活性的增加。此外，BMDM-HG-exo通过增加糖酵解活性诱导细胞增殖和重编程能量代谢。最后，分析来自患有晚期动脉粥样硬化的糖尿病受试者的BMDM-HG-exo和血浆EV中的microRNA聚集在miR-486- 5 p上，miR-486- 5 p通常在造血失调和Abca 1对照中富集和识别。总之，我们的研究结果表明，电动汽车有助于传达高血糖症的有害特性，加速糖尿病患者的动脉粥样硬化。在高葡萄糖（HG）中培养的巨噬细胞产生促动脉粥样硬化外泌体HG外泌体驱动受体巨噬细胞中的糖酵解和Apoe-/-小鼠中的单核细胞增多HG巨噬细胞外泌体和人糖尿病PAD血浆EV富含miR-486- 5 p内分泌系统生理学;细胞生物学
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. 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-486-5p Endocrine system physiology; Cell biology
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影响因子：
3.7
作者：
Duong, Phat;Chung, Allen;Raffai, Robert L.
通讯作者：
Raffai, Robert L.
影响因子：
6
作者：
Gaudreault, Nathalie;Kumar, Nikit;Raffai, Robert L.
通讯作者：
Raffai, Robert L.
DOI：
10.1016/j.bbrc.2015.11.128
发表时间：
2016-04-08
影响因子：
3.1
作者：
Liu, Dan;Zhang, Min;Tang, Chao-Ke
通讯作者：
Tang, Chao-Ke
影响因子：
7.7
作者：
Kanter, Jenny E.;Kramer, Farah;Bornfeldt, Karin E.
通讯作者：
Bornfeldt, Karin E.
血浆来源的外泌体特征揭示了长持续时间1型糖尿病中明显的microRNA特征。
影响因子：
4.6
作者：
Garcia-Contreras M;Shah SH;Tamayo A;Robbins PD;Golberg RB;Mendez AJ;Ricordi C
通讯作者：
Ricordi C