Evidence for Adipocyte-Derived Extracellular Vesicles in the Human Circulation

Connolly, Katherine; Wadey, Rebecca M.; Mathew, Donna; Johnson, Errin; Rees, Dafydd Aled; James, Philip E.

doi:10.1210/en.2018-00266

Cited by 37 publications

(35 citation statements)

References 33 publications

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“…Despite their morphologic heterogeneity, they are characterized as small EVs with a cup shape and a size of 50-150 nm in diameter in transmission electron microscopy observations. Although the MAT explant EVs are likely a product of EV secretion from multiple cell types, we further confirmed the presence of adipocytespecific marker PLIN in MAT-EVs (22,47) and showed evidence that EVs are released from MAT-Ad and 3T3-Ad. Moreover, these secreted EVs, along with their cargos (herein miRNAs), can be taken up into SMCs, mimicking the transport of EV messenger molecules from adventitial adipocytes to adjacent medial SMCs.…”

Section: Pvat During Inflammation Secretes Mir-221-3p-containing Evssupporting

confidence: 66%

Perivascular adipose tissue–derived extracellular vesicle miR‐221‐3p mediates vascular remodeling

Ballantyne²,

et al. 2019

The FASEB Journal

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Adipose tissue–secreted extracellular vesicles (EVs) containing microRNAs (miRNAs) convey intercellular message signaling. The biogenesis of EV‐miRNAs from perivascular adipose tissue (PVAT) and their roles in intercellular communication in response to obesity‐associated inflammation have not yet been fully explored. By feeding mice a high‐fat diet for 16 wk, we established obesity‐associated, chronic low‐grade inflammation in PVAT, characterized as hypertrophy of perivascular adipocytes, decreased adipogenesis, and proinflammatory macrophage infiltration. We show that PVAT‐derived EVs and their encapsulated miRNAs can be taken up into vascular smooth muscle cells (VSMCs) in vivo and in vitro. miR‐221‐3p is one of the highly enriched miRNAs in obese PVAT and PVAT‐derived EVs. Transfer and direct overexpression of miR‐221‐3p dramatically enhances VSMC proliferation and migration. Peroxisome proliferator–activated receptor γ coactivator 1α is identified as a miR‐221‐3p target in VSMC phenotypic modulation. Obese mice secrete abundant miRNA‐containing EVs, evoking inflammatory responses in PVAT and vascular phenotypic switching in abdominal aorta of lean mice. Local delivery of miR‐221‐3p mimic in femoral artery causes vascular dysfunction by suppressing the contractile genes in the arterial wall. Our findings provide an EV–miR‐221‐3p–mediated mechanism by which PVAT triggers an early‐stage vascular remodeling in the context of obesity‐associated inflammation.—Li, X., Ballantyne, L. L., Yu, Y., Funk, C. D. Perivascular adipose tissue–derived extracellular vesicle miR‐221‐3p mediates vascular remodeling. FASEB J. 33, 12704–12722 (2019). http://www.fasebj.org

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Section: Pvat During Inflammation Secretes Mir-221-3p-containing Evssupporting

confidence: 66%

Perivascular adipose tissue–derived extracellular vesicle miR‐221‐3p mediates vascular remodeling

Ballantyne²,

et al. 2019

The FASEB Journal

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“…TEM is the goal standard method for imaging EVs and is present in a majority of EVs studies . Due to its high resolution, it allows determining the size and morphology of single vesicles.…”

Section: Methodological Guidelines For Evs Researchmentioning

confidence: 99%

Application of Extracellular Vesicles Proteomics to Cardiovascular Disease: Guidelines, Data Analysis, and Future Perspectives

et al. 2019

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Extracellular vesicles (EVs) are a heterogeneous population of vesicles composed of a lipid bilayer that carry a large repertoire of molecules including proteins, lipids, and nucleic acids. In this review, some guidelines for plasma‐derived EVs isolation, characterization, and proteomic analysis, and the application of the above to cardiovascular disease (CVD) studies are provided. For EVs analysis, blood samples should be collected using a 21‐gauge needle, preferably in citrate tubes, and plasma stored for up to 1 year at −80°, using a single freeze–thaw cycle. For proteomic applications, differential centrifugation (including ultracentrifugation steps) is a good option for EVs isolation. EVs characterization is done by transmission electron microscopy, particle enumeration techniques (nanoparticle‐tracking analysis, dynamic light scattering), and flow cytometry. Regarding the proteomics strategy, a label‐free and gel‐free quantitative method is a good choice due to its accuracy and because it minimizes the amount of sample required for clinical applications. Besides the above, main EVs proteomic findings in cardiovascular‐related diseases are presented and analyzed in this review, paying especial attention to overlapping results between studies. The latter might offer new insights into the clinical relevance and potential of novel EVs biomarkers identified to date in the context of CVD.

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“…In addition to SkM explants, WAT explants have also been studied. EVs expressing a white adipocyte profile for adipokines and adipocyte-derived proteins have been found in human plasma (3). In addition, the WAT explant model has been employed to characterize adipocytespecific EV-like particles (5).…”

Section: Background and Rationalementioning

confidence: 99%

Skeletal muscle tissue secretes more extracellular vesicles than white adipose tissue and myofibers are a major source ex vivo but not in vivo

Estrada

Valenti

Hehn

et al. 2020

Preprint

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Circulating extracellular vesicles (EVs) are biomarkers of and contributors to the etiology of disease. Skeletal muscle (SkM) and white adipose tissue (WAT) are the two largest organs by mass in humans and rodents but the relative contribution of EVs from these tissues is unknown. We hypothesized that SkM tissue secretes more EVs than WAT and that a dual fluorescent reporter mouse could be used to detect SkM myofiber-derived EVs in vivo. Human Protein Atlas data and directly measuring EV secretion in mouse SkM and WAT using an ex vivo tissue explant model confirmed that SkM tissue secretes more EVs than WAT. Differences in EV secretion between SkM and WAT were not due to SkM contraction but may be explained by differences in tissue metabolic capacity. A SkM myofiber-specific dual fluorescent reporter mouse was created. Spectral flow cytometry revealed that SkM myofibers are a major source of SkM tissue-derived EVs ex vivo but few reach the circulation in vivo. Our findings demonstrate that SkM secretes more EVs than WAT and many come from SkM myofibers, but our in vivo data indicate that EVs secreted by SkM myofibers may remain primarily in their local extracellular environment.

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Evidence for Adipocyte-Derived Extracellular Vesicles in the Human Circulation

Cited by 37 publications

References 33 publications

Perivascular adipose tissue–derived extracellular vesicle miR‐221‐3p mediates vascular remodeling

Perivascular adipose tissue–derived extracellular vesicle miR‐221‐3p mediates vascular remodeling

Application of Extracellular Vesicles Proteomics to Cardiovascular Disease: Guidelines, Data Analysis, and Future Perspectives

Skeletal muscle tissue secretes more extracellular vesicles than white adipose tissue and myofibers are a major source ex vivo but not in vivo

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