Extracellular vesicles in cardiovascular homeostasis and disease

Hutcheson, Joshua D.; Aikawa, Elena

doi:10.1097/hco.0000000000000510

Cited by 46 publications

(42 citation statements)

References 35 publications

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“…Multivesicular cargos ( Figure 1A-D) have also been described as EVs with a particular appearance: clustered vesicles (80-200 nm) shielded by plasma membrane [18]. This type of EVs has been described as mediating bone mineralization [19], vascular calcifications [20], or intercellular communication between telocytes [18], which often surround the vessels [21]. In our experience, endothelial cells (ECs) from diabetic kidney often release multivesicular cargos in the vascular lumen ( Figure 1C).…”

Section: Terminology and Biogenesis Pathways Of Extracellular Vesiclesmentioning

confidence: 84%

“…EVs found in intima and media of calcified vascular wall (Figure 2A-D) [14] seem to be different of matrix vesicle with role in physiological and pathological calcification [19]. Vascular cell-derived EVs may serve as a continuous source of damaging microcalcifications in atherosclerotic plaques [20]. These vesicles have been described as exosomes from endosomal compartment, plasma membranederived ectosomes, and vesicles shielded by a plasma membrane (multivesicular cargos) that are released into extracellular space as a cargo [14].…”

Section: Atherosclerosis and Vascular Calcification In Diabetes Mellitusmentioning

confidence: 99%

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Part One: Extracellular Vesicles as Valuable Players in Diabetic Cardiovascular Diseases

Gherghiceanu¹,

Alexandru²,

Magda³

et al. 2020

Extracellular Vesicles and Their Importance in Human Health

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Extracellular vesicles (EVs) are particles released in the extracellular space from all cell types in physiological and pathological conditions and emerge as a new way of cell-cell communication by transferring their biological contents into target cells. The levels and composition of circulating EVs differ from a normal condition to a pathological one, making them real circulating biomarkers. EVs have a very complex contribution in both health and disease, most likely in relationship between diabetes and cardiovascular disease. The involvement of EVs to the development of cardiovascular complications in diabetes remains an open discussion for therapists. Circulating EVs may offer a continuous access path to circulating information on the disease state and a new perspective in finding a correct diagnosis, in estimating a prognosis and also in applying an effective therapy. Besides their role as biomarkers and targets for therapy, EVs can be exploited as biological tools in influencing the different processes affected in diabetic cardiovascular diseases. This chapter will summarize the current knowledge about EVs as biological vectors modulating diabetic cardiovascular diseases, including atherosclerosis, coronary artery disease, and peripheral arterial disease. Finally, we will point out EVs' considerable value as clinical biomarkers, therapeutic targets, and potential biomedical tools for the discovery of effective therapy in diabetic cardiovascular diseases.

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Section: Terminology and Biogenesis Pathways Of Extracellular Vesiclesmentioning

confidence: 84%

Section: Atherosclerosis and Vascular Calcification In Diabetes Mellitusmentioning

confidence: 99%

Part One: Extracellular Vesicles as Valuable Players in Diabetic Cardiovascular Diseases

Gherghiceanu¹,

Alexandru²,

Magda³

et al. 2020

Extracellular Vesicles and Their Importance in Human Health

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“…Bacterial vesicles could induce immune reactions in host cells (15,16). They can interact with innate immune cells, e.g., macrophages and neutrophils, as well as adaptive immune cells and antigen-presenting cells (APCs), e.g., dendritic cells (DCs).…”

Section: Introductionmentioning

confidence: 99%

Streptococcal Extracellular Membrane Vesicles Are Rapidly Internalized by Immune Cells and Alter Their Cytokine Release

et al. 2020

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Extracellular vesicles are membranous structures shed by almost every living cell. Bacterial gram-negative outer membrane vesicles (OMVs) and gram-positive membrane vesicles (MVs) play important roles in adaptation to the surrounding environment, cellular components' exchange, transfer of antigens and virulence factors, and infection propagation. Streptococcus pneumoniae is considered one of the priority pathogens, with a global health impact due to the increase in infection burden and growing antibiotic resistance. We isolated MVs produced from the S. pneumoniae reference strain (R6) and purified them via size exclusion chromatography (SEC) to remove soluble protein impurities. We characterized the isolated MVs by nanoparticle tracking analysis (NTA) and measured their particle size distribution and concentration. Isolated MVs showed a mean particle size range of 130-160 nm and a particle yield of around 10 12 particles per milliliter. Cryogenic transmission electron microscopy (cryo-TEM) images revealed a very heterogeneous nature of isolated MVs with a broad size range and various morphologies, arrangements, and contents. We incubated streptococcal MVs with several mammalian somatic cells, namely, human lung epithelial A549 and human keratinocytes HaCaT cell lines, and immune cells including differentiated macrophage-like dTHP-1 and murine dendritic DC2.4 cell lines. All cell lines displayed excellent viability profile and negligible cytotoxicity after 24-h incubation with MVs at concentrations reaching 10 6 MVs per cell (somatic cells) and 10 5 MVs per cell (immune cells). We evaluated the uptake of fluorescently labeled MVs into these four cell lines, using flow cytometry and confocal microscopy. Dendritic cells demonstrated prompt uptake after 30-min incubation, whereas other cell lines showed increasing uptake after 2-h incubation and almost complete colocalization/internalization of MVs after only 4-h incubation. We assessed the influence of streptococcal MVs on antigen-presenting cells, e.g., dendritic cells, using enzyme-linked immunosorbent assay (ELISA) and observed enhanced release of tumor necrosis factor (TNF)-α, a slight increase of interleukin (IL)-10 Mehanny et al. Streptococcal Membrane Vesicles secretion, and no detectable effect on IL-12. Our study provides a better understanding of gram-positive streptococcal MVs and shows their potential to elicit a protective immune response. Therefore, they could offer an innovative avenue for safe and effective cell-free vaccination against pneumococcal infections.

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“…In addition to proteins exiting the cell by classical secretory pathways, muscle cells also release protein-associated vesicles [5]. These extracellular vesicles (EVs) are widely studied in different physiological and pathological contexts, and are known to play a key role in tissue homeostasis [8], embryogenesis and development [9], cell survival [10], inflammatory and metabolic diseases [11,12], cancer metastasis [13]. EVs are broadly classified as exosomes, ectosomes or apoptotic bodies.…”

Section: Introductionmentioning

confidence: 99%

Optimized method for extraction of exosomes from human primary muscle cells

Gall

Ouandaogo

Anakor

et al. 2020

Preprint

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wordsSkeletal muscle is increasingly considered as an endocrine organ secreting myokines and extracellular vesicles (exosomes and microvesicles), which can effect physiological changes with impact in different pathological conditions, including regenerative processes, aging and myopathies. Primary human myoblasts are an essential tool to study the muscle vesicle secretome. Since their differentiation in conditioned media does not induce any signs of cell death or cell stress, artefactual effects from those processes are unlikely. However, adult human primary myoblasts senesce in long-term tissue culture, so a major technical challenge is posed by the need to avoid artefactual effects resulting from pre-senescent changes. Since these cells should be studied within a strictly controlled pre-senescent division count (<21 divisions), and yields of myoblasts per muscle biopsy are low, it is difficult or impossible to amplify sufficiently large cell numbers (some 250 x 10 6 myoblasts) to obtain sufficient conditioned medium for the standard ultracentrifugation approach to exosome isolation.Thus an optimized strategy to extract and study secretory muscle vesicles is needed. In this study, conditions are optimized for the in vitro cultivation of human myoblasts, and the quality and yield of exosomes extracted using an ultracentrifugation protocol are compared with a modified polymer-based precipitation strategy combined with extra washing steps. Both vesicle

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Extracellular vesicles in cardiovascular homeostasis and disease

Cited by 46 publications

References 35 publications

Part One: Extracellular Vesicles as Valuable Players in Diabetic Cardiovascular Diseases

Part One: Extracellular Vesicles as Valuable Players in Diabetic Cardiovascular Diseases

Streptococcal Extracellular Membrane Vesicles Are Rapidly Internalized by Immune Cells and Alter Their Cytokine Release

Optimized method for extraction of exosomes from human primary muscle cells

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