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High Glucose Macrophage Exosomes Enhance Atherosclerosis by Driving Cellular Proliferation & Hematopoiesis [miRNA-Seq]

ABSTRACT: High Glucose Macrophage Exosomes Enhance Atherosclerosis by Driving Cellular Proliferation & Hematopoiesis [miRNA-Seq]

PROVIDER: PRJNA683909 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13234142.fastq.gz	Fastqsanger.gz
	SRR13234143.fastq.gz	Fastqsanger.gz
	SRR13234144.fastq.gz	Fastqsanger.gz
	SRR13234145.fastq.gz	Fastqsanger.gz
	SRR13234146.fastq.gz	Fastqsanger.gz

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High Glucose Macrophage Exosomes Enhance Atherosclerosis by Driving Cellular Proliferation & Hematopoiesis

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High Glucose Macrophage Exosomes Enhance Atherosclerosis by Driving Cellular Proliferation & Hematopoiesis [RNA-Seq]

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High Glucose Macrophage Exosomes Enhance Atherosclerosis by Driving Cellular Proliferation & Hematopoiesis [RNA-Seq]

Project description:Hyperglycemia is a recognized risk factor for cardiovascular complications in diabetes. While hyperglycemia is known to cause microRNA dysregulation that contributes to cellular activation, whether it can do so through intercellular communication via extracellular vesicles (EVs) is not known. We investigated whether 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. Repeated infusion of BMDM–HG-exo led to a robust increase in hematopoiesis leading to augmented circulating myeloid cell numbers. Four weeks of BMDM–HG-exo infusions increased atherosclerotic lesion sizes with an accumulation of macrophage and apoptotic cells in the aortic root. Transcriptome-wide analysis of naïve cultured macrophages treated with BMDM–HG-exo showed an upregulation of genes associated with cell proliferation. Furthermore, BMDM–HG-exo reprogramed energy metabolism in recipient macrophages with an upregulation of glycolytic activity. Plasma EVs isolated from human subjects with type II diabetes exerted similar cell signaling when incubated with cultured human macrophages. Lastly, profiling microRNA in BMDM–HG-exo and human diabetic plasma EVs converged on miR-486 as commonly enriched. In conclusion, our findings show that EVs serve to communicate detrimental

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High Glucose Macrophage Exosomes Enhance Atherosclerosis by Driving Cellular Proliferation & Hematopoiesis [miRNA-Seq]

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

Project description: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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Macrophage Exosomes Resolve Atherosclerosis by Regulating Hematopoiesis and Inflammation via MicroRNA Cargo

Project description:Developing strategies that promote the resolution of vascular inflammation and atherosclerosis remains a major therapeutic challenge. Here, we show that exosomes produced by naive bone marrow-derived macrophages (BMDM-exo) contain anti-inflammatory microRNA-99a/146b/378a that are further increased in exosomes produced by BMDM polarized with IL-4 (BMDM-IL-4-exo). These exosomal microRNAs suppress inflammation by targeting NF-kB and TNF-a signaling and foster M2 polarization in recipient macrophages. Repeated infusions of BMDM-IL-4-exo into Apoe_x0001_/_x0001_ mice fed a Western diet reduce excessive hematopoiesis in the bone marrow and thereby the number of myeloid cells in the circulation and macrophages in aortic root lesions. This also leads to a reduction in necrotic lesion areas that collectively stabilize atheroma. Thus, BMDM-IL-4-exo may represent a useful therapeutic approach for atherosclerosis and other inflammatory disorders by targeting NF-kB and TNF-a via microRNA cargo delivery.

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High Glucose Macrophage Exosomes Enhance Atherosclerosis by Driving Cellular Proliferation & Hematopoiesis

Project description:This SuperSeries is composed of the SubSeries listed below.

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