Extracellular Vesicles Secreted by Atherogenic Macrophages Transfer MicroRNA to Inhibit Cell Migration

Nguyen, My Anh; Karunakaran, Denuja; Geoffrion, Michèle; Cheng, Henry S.; Tandoc, Kristofferson; Matic, Ljubica; Hedin, Ulf; Maegdefessel, Lars; Fish, Jason E.; Rayner, Katey J.

doi:10.1161/atvbaha.117.309795

Cited by 200 publications

(156 citation statements)

References 67 publications

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“…Extracellular vesicles (EVs) are now recognized as having an important role in intercellular communication and, contrary to previous beliefs, are not insignificant cellular debris that accumulates with membrane shedding (16)(17)(18). Currently, EVs are classified into 3 main groups, based largely on a specific set of criteria: size, density, protein/lipid composition, and the process underlying release (17,19,20).…”

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Characterization of heat shock protein 27 in extracellular vesicles: a potential anti‐inflammatory therapy

et al. 2018

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Previously, we reported that elevated serum levels of heat shock protein 27 (HSP27) are predictive of a lower risk of having a heart attack, stroke, or death from cardiovascular disease. Moreover, augmenting HSP27 (or the murine ortholog, HSP25) attenuated experimental atherogenesis, reduced inflammation, and lowered cholesterol levels. Recently, we noted that HSP27 activates NF-κB via TLR-4, resulting in attenuation of plaque inflammation; however, the precise anti-atherosclerosis mechanisms mediated by extracellular HSP27 are incompletely understood. Our purpose in this study was to investigate the existence of HSP27 in extracellular vesicles (EVs) and whether HSP27 elicited atheroprotective effects on target cells. Here, we provide evidence that HSP27 localizes to EVs derived from THP-1 cells using transmission electron microscopy (TEM) and immunogold labeling, Western blotting, ELISA, and fluorescence-activated cell sorting. TEM imaging indicated that HSP27 is found at the exosomal membrane. Multiple reactor monitor-mass spectrometric analysis of large vesicles, which included microparticles and exosomes, isolated from human plasma, also led to detection of HSP27 using the unique signature peptide, R.LFDQAFGLPR.L. Studies using THP-1 and human embryonic kidney cells show that HSP27-laden exosomes significantly stimulated NF-κB activation ( P < 0.001) and release of IL-10 ( P < 0.0001), suggesting that HSP27 may be important exosomal cargo with beneficial anti-inflammatory effects.-Shi, C., Ulke-Lemée, A., Deng, J., Batulan, Z., O'Brien, E. R. Characterization of heat shock protein 27 in extracellular vesicles: a potential anti-inflammatory therapy.

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Characterization of heat shock protein 27 in extracellular vesicles: a potential anti‐inflammatory therapy

et al. 2018

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“…In another study, exosomes secreted by atherogenic macrophages were shown to be able to transfer specific microRNAs, including miR‐146a, to naïve macrophages. Treatment with these exosomes could inhibit the migratory activity of the naïve macrophages, potentially promoting macrophage entrapment in the vessel wall and atherosclerosis …”

Section: Role Of Exosomesmentioning

confidence: 99%

Exosomes in Inflammation and Inflammatory Disease

et al. 2019

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Exosomes are a subset of extracellular vesicles released by all cell types and involved in local and systemic intercellular communication. In the past decade, research into exosomes has swelled as their important role in the mediation of health and disease has been increasingly established and acknowledged. Exosomes carry a diverse range of cargo including proteins, nucleic acids, and lipids derived from their parental cell that, when delivered to the recipient cell, can confer pathogenic or therapeutic effects through modulation of immunity and inflammation. In this review, the role of exosomes on mediation of immune and inflammatory responses, and their participation in diseases with a significant inflammatory component is discussed. The considerable potential for exosomes in therapy and diagnosis of inflammatory diseases is also highlighted.

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“…Human monocytes can secrete microvesicles containing miRNAs that are uptaken by endothelial cells and increase their migratory capabilities [127]. MiR-150 is contained in monocyte-derived microvesicles, both from the monocytic cell line, THP1, and from human peripheral blood monocytes [60].…”

Section: Control Of Leukocyte Trafficking and Inflammationmentioning

confidence: 99%

MicroRNAs in endothelial cell homeostasis and vascular disease

Fernández‐Hernando

Suárez²

2018

Current Opinion in Hematology

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Purpose of review Since the first discovery of microRNAs (miRNAs) in 1993, the involvement of miRNAs in different aspects of vascular disease has emerged as an important research field. In this review, we summarize the fundamental roles of miRNAs in controlling endothelial cell functions and their implication with several aspects of vascular dysfunction. Recent findings MiRNAs have been found to be critical modulators of endothelial homeostasis. The dysregulation of miRNAs has been linked to endothelial dysfunction and the development and progression of vascular disease which and open new opportunities of using miRNAs as potential therapeutic targets for vascular disease. Summary Further determination of miRNA regulatory circuits and defining miRNAs-specific target genes remains key to future miRNA-based therapeutic applications toward vascular disease prevention. Many new and unanticipated roles of miRNAs in the control of endothelial functions will assist clinicians and researchers in developing potential therapeutic applications.

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Extracellular Vesicles Secreted by Atherogenic Macrophages Transfer MicroRNA to Inhibit Cell Migration

Abstract: EV-derived miRNAs from atherogenic macrophages, in particular miR-146a, may accelerate the development of atherosclerosis by decreasing cell migration and promoting macrophage entrapment in the vessel wall.

Cited by 200 publications

References 67 publications

Characterization of heat shock protein 27 in extracellular vesicles: a potential anti‐inflammatory therapy

Characterization of heat shock protein 27 in extracellular vesicles: a potential anti‐inflammatory therapy

Exosomes in Inflammation and Inflammatory Disease

MicroRNAs in endothelial cell homeostasis and vascular disease

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