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Thrombo-Inflammatory Extracellular Vesicles

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 17149

Special Issue Editors

Centro Dipartimentale di Biologia Cellulare Cardiorespiratoria, Dipartimento di Patologia Chirurgica, Medica, Molecolare e di Area Critica e Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy
Interests: extracellular vesicles; microparticles; mechanism underlying microparticle generation; intercellular communication; inflammatory markers; miRNAs; lung inflammation; lung diseases
Special Issues, Collections and Topics in MDPI journals
SC Pneumologia, Ospedale di Lucca, USL Toscana Nord-Ovest, Lucca, Italy
Interests: extracellular vesicles; chronic obstructive pulmonary disease; lung inflammation; venous thromboembolism
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The term “extracellular vesicles” (EV) refers to particles naturally released by several cell types upon different stimuli, which are bounded by a lipid bilayer and cannot replicate. Exosomes, microparticles, and apoptotic bodies, which differ in composition, biogenesis, and size, belong to this family. Evidence gathered over the past several years has demonstrated that EV are involved in numerous physiological processes, including blood coagulation and inflammation. Initially proposed as actors in blood coagulation, more recently, it has become evident that EV also carry other biological components of the parental cell in addition to phospholipids, which greatly broaden the spectrum of their potential effects as intercellular mediators and players in pathological processes.

For this Special Issue, we invite researchers to contribute either with original research (both in vivo or in vitro studies) or review articles focusing on vesicle-mediated thrombo-inflammatory mechanisms, as well as on the potential role of these EV as biomarkers, in the pathophysiology of cardiovascular and respiratory diseases.

Dr. Tommaso Neri
Dr. Dario Nieri
Guest Editors

Manuscript Submission Information

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Keywords

  • Extracellular vesicles
  • Inflammation
  • Thrombosis
  • Airway diseases
  • Cardiovascular diseases
  • Biomarkers
  • EV mechanisms of action

Published Papers (6 papers)

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Research

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21 pages, 4820 KiB  
Article
Extracellular Vesicles Mediate Communication between Endothelial and Vascular Smooth Muscle Cells
by Marie Fontaine, Stéphanie Herkenne, Olivier Ek, Alicia Paquot, Amandine Boeckx, Cécile Paques, Olivier Nivelles, Marc Thiry and Ingrid Struman
Int. J. Mol. Sci. 2022, 23(1), 331; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23010331 - 28 Dec 2021
Cited by 11 | Viewed by 1848
Abstract
The recruitment of pericytes and vascular smooth muscle cells (SMCs) that enwrap endothelial cells (ECs) is a crucial process for vascular maturation and stabilization. Communication between these two cell types is crucial during vascular development and in maintaining vessel homeostasis. Extracellular vesicles (EVs) [...] Read more.
The recruitment of pericytes and vascular smooth muscle cells (SMCs) that enwrap endothelial cells (ECs) is a crucial process for vascular maturation and stabilization. Communication between these two cell types is crucial during vascular development and in maintaining vessel homeostasis. Extracellular vesicles (EVs) have emerged as a new communication tool involving the exchange of microRNAs between cells. In the present study, we searched for microRNAs that could be transferred via EVs from ECs to SMCs and vice versa. Thanks to a microRNA profiling experiment, we found that two microRNAs are more exported in each cell type in coculture experiments: while miR-539 is more secreted by ECs, miR-582 is more present in EVs from SMCs. Functional assays revealed that both microRNAs can modulate both cell-type phenotypes. We further identified miR-539 and miR-582 targets, in agreement with their respective cell functions. The results obtained in vivo in the neovascularization model suggest that miR-539 and miR-582 might cooperate to trigger the process of blood vessel coverage by smooth muscle cells in a mature plexus. Taken together, these results are the first to highlight the role of miR-539 and miR-582 in angiogenesis and communication between ECs and SMCs. Full article
(This article belongs to the Special Issue Thrombo-Inflammatory Extracellular Vesicles)
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17 pages, 8697 KiB  
Article
Effects of Microvesicles Derived from NK Cells Stimulated with IL-1β on the Phenotype and Functional Activity of Endothelial Cells
by Kseniia Markova, Valentina Mikhailova, Yulia Milyutina, Andrey Korenevsky, Anastasia Sirotskaya, Veronika Rodygina, Elizaveta Tyshchuk, Polina Grebenkina, Andrey Simbirtsev, Sergey Selkov and Dmitry Sokolov
Int. J. Mol. Sci. 2021, 22(24), 13663; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222413663 - 20 Dec 2021
Cited by 5 | Viewed by 2541
Abstract
Microvesicles (MVs) are plasma extracellular vesicles ranging from 100 (150) to 1000 nm in diameter. These are generally produced by different cells through their vital activity and are a source of various protein and non-protein molecules. It is assumed that MVs can mediate [...] Read more.
Microvesicles (MVs) are plasma extracellular vesicles ranging from 100 (150) to 1000 nm in diameter. These are generally produced by different cells through their vital activity and are a source of various protein and non-protein molecules. It is assumed that MVs can mediate intercellular communication and modulate cell functions. The interaction between natural killer cells (NK cells) and endothelial cells underlies multiple pathological conditions. The ability of MVs derived from NK cells to influence the functional state of endothelial cells in inflammatory conditions has yet to be studied well. In this regard, we aimed to study the effects of MVs derived from NK cells of the NK-92 cell line stimulated with IL-1β on the phenotype, caspase activity, proliferation and migration of endothelial cells of the EA.hy926 cell line. Endothelial cells were cultured with MVs derived from cells of the NK-92 cell line after their stimulation with IL-1β. Using flow cytometry, we evaluated changes in the expression of endothelial cell surface molecules and endothelial cell death. We evaluated the effect of MVs derived from stimulated NK cells on the proliferative and migratory activity of endothelial cells, as well as the activation of caspase-3 and caspase-9 therein. It was established that the incubation of endothelial cells with MVs derived from cells of the NK-92 cell line stimulated with IL-1β and with MVs derived from unstimulated NK cells, leads to the decrease in the proliferative activity of endothelial cells, appearance of the pan leukocyte marker CD45 on them, caspase-3 activation and partial endothelial cell death, and reduced CD105 expression. However, compared with MVs derived from unstimulated NK cells, a more pronounced effect of MVs derived from cells of the NK-92 cell line stimulated with IL-1β was found in relation to the decrease in the endothelial cell migratory activity and the intensity of the CD54 molecule expression on them. The functional activity of MVs is therefore mediated by the conditions they are produced under, as well as their internal contents. Full article
(This article belongs to the Special Issue Thrombo-Inflammatory Extracellular Vesicles)
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11 pages, 2016 KiB  
Article
Procoagulant Extracellular Vesicles Alter Trophoblast Differentiation in Mice by a Thrombo-Inflammatory Mechanism
by Paulina Markmeyer, Franziska Lochmann, Kunal Kumar Singh, Anubhuti Gupta, Ruaa Younis, Khurrum Shahzad, Ronald Biemann, Hanna Huebner, Matthias Ruebner, Berend Isermann and Shrey Kohli
Int. J. Mol. Sci. 2021, 22(18), 9873; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22189873 - 13 Sep 2021
Cited by 3 | Viewed by 1874
Abstract
Procoagulant extracellular vesicles (EV) and platelet activation have been associated with gestational vascular complications. EV-induced platelet-mediated placental inflammasome activation has been shown to cause preeclampsia-like symptoms in mice. However, the effect of EV-mediated placental thrombo-inflammation on trophoblast differentiation remains unknown. Here, we identify [...] Read more.
Procoagulant extracellular vesicles (EV) and platelet activation have been associated with gestational vascular complications. EV-induced platelet-mediated placental inflammasome activation has been shown to cause preeclampsia-like symptoms in mice. However, the effect of EV-mediated placental thrombo-inflammation on trophoblast differentiation remains unknown. Here, we identify that the EV-induced thrombo-inflammatory pathway modulates trophoblast morphology and differentiation. EVs and platelets reduce syncytiotrophoblast differentiation while increasing giant trophoblast and spongiotrophoblast including the glycogen-rich cells. These effects are platelet-dependent and mediated by the NLRP3 inflammasome. In humans, inflammasome activation was negatively correlated with trophoblast differentiation marker GCM1 and positively correlated with blood pressure. These data identify a crucial role of EV-induced placental thrombo-inflammation on altering trophoblast differentiation and suggest platelet activation or inflammasome activation as a therapeutic target in order to achieve successful placentation. Full article
(This article belongs to the Special Issue Thrombo-Inflammatory Extracellular Vesicles)
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Review

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16 pages, 1069 KiB  
Review
Extracellular Vesicles and Thrombogenicity in Atrial Fibrillation
by Alexander E. Berezin and Alexander A. Berezin
Int. J. Mol. Sci. 2022, 23(3), 1774; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23031774 - 04 Feb 2022
Cited by 10 | Viewed by 2272
Abstract
Extracellular vesicles (EVs) are defined as a heterogenic group of lipid bilayer vesicular structures with a size in the range of 30–4000 nm that are released by all types of cultured cells. EVs derived from platelets, mononuclears, endothelial cells, and adipose tissue cells [...] Read more.
Extracellular vesicles (EVs) are defined as a heterogenic group of lipid bilayer vesicular structures with a size in the range of 30–4000 nm that are released by all types of cultured cells. EVs derived from platelets, mononuclears, endothelial cells, and adipose tissue cells significantly increase in several cardiovascular diseases, including in atrial fibrillation (AF). EVs are engaged in cell-to-cell cooperation, endothelium integrity, inflammation, and immune response and are a cargo for several active molecules, such as regulatory peptides, receptors, growth factors, hormones, and lipids. Being transductors of the intercellular communication, EVs regulate angiogenesis, neovascularization, coagulation, and maintain tissue reparation. There is a large amount of evidence regarding the fact that AF is associated with elevated levels of EVs derived from platelets and mononuclears and a decreased number of EVs produced by endothelial cells. Moreover, some invasive procedures that are generally performed for the treatment of AF, i.e., pulmonary vein isolation, were found to be triggers for elevated levels of platelet and mononuclear EVs and, in turn, mediated the transient activation of the coagulation cascade. The review depicts the role of EVs in thrombogenicity in connection with a risk of thromboembolic complications, including ischemic stroke and systemic thromboembolism, in patients with various forms of AF. Full article
(This article belongs to the Special Issue Thrombo-Inflammatory Extracellular Vesicles)
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24 pages, 36018 KiB  
Review
Epithelial-Cell-Derived Extracellular Vesicles in Pathophysiology of Epithelial Injury and Repair in Chronic Rhinosinusitis: Connecting Immunology in Research Lab to Biomarkers in Clinics
by Toru Takahashi and Robert P Schleimer
Int. J. Mol. Sci. 2021, 22(21), 11709; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111709 - 28 Oct 2021
Cited by 7 | Viewed by 3197
Abstract
Epithelial barrier disruption and failure of epithelial repair by aberrant epithelial-mesenchymal transition (EMT)-induced basal cells observed in nasal mucosa of chronic rhinosinusitis (CRS) are speculated to play important roles in disease pathophysiology. Microparticles (MPs) are a type of extracellular vesicle (EV) released by [...] Read more.
Epithelial barrier disruption and failure of epithelial repair by aberrant epithelial-mesenchymal transition (EMT)-induced basal cells observed in nasal mucosa of chronic rhinosinusitis (CRS) are speculated to play important roles in disease pathophysiology. Microparticles (MPs) are a type of extracellular vesicle (EV) released by budding or shedding from the plasma membrane of activated or apoptotic cells. MPs are detected in nasal lavage fluids (NLFs) and are now receiving attention as potential biomarkers to evaluate the degree of activation of immune cells and injury of structural cells in nasal mucosa of subjects with sinus disease. There are three types of epithelial-cell-derived MPs, which are defined by the expression of different epithelial specific markers on their surface: EpCAM, E-cadherin, and integrin β6 (ITGB6). When these markers are on MPs that are also carrying canonical EMT/mesenchymal markers (Snail (SNAI1); Slug (SNAI2); alpha-smooth muscle actin (αSMA, ACTA2)) or pro- and anti-coagulant molecules (tissue factor (TF); tissue plasminogen activator (tPA); plasminogen activator inhibitor-1 (PAI-1)), they provide insight as to the roles of epithelial activation for EMT or regulation of coagulation in the underlying disease. In this review, we discuss the potential of epithelial MPs as research tools to evaluate status of nasal mucosae of CRS patients in the lab, as well as biomarkers for management and treatment of CRS in the clinic. Full article
(This article belongs to the Special Issue Thrombo-Inflammatory Extracellular Vesicles)
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13 pages, 1660 KiB  
Review
Critical Review of the Evolution of Extracellular Vesicles’ Knowledge: From 1946 to Today
by Erica Bazzan, Mariaenrica Tinè, Alvise Casara, Davide Biondini, Umberto Semenzato, Elisabetta Cocconcelli, Elisabetta Balestro, Marco Damin, Claudia Maria Radu, Graziella Turato, Simonetta Baraldo, Paolo Simioni, Paolo Spagnolo, Marina Saetta and Manuel G. Cosio
Int. J. Mol. Sci. 2021, 22(12), 6417; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22126417 - 15 Jun 2021
Cited by 65 | Viewed by 4433
Abstract
Extracellular vesicles (EVs) are a family of particles/vesicles present in blood and body fluids, composed of phospholipid bilayers that carry a variety of molecules that can mediate cell communication, modulating crucial cell processes such as homeostasis, induction/dampening of inflammation, and promotion of repair. [...] Read more.
Extracellular vesicles (EVs) are a family of particles/vesicles present in blood and body fluids, composed of phospholipid bilayers that carry a variety of molecules that can mediate cell communication, modulating crucial cell processes such as homeostasis, induction/dampening of inflammation, and promotion of repair. Their existence, initially suspected in 1946 and confirmed in 1967, spurred a sharp increase in the number of scientific publications. Paradoxically, the increasing interest for EV content and function progressively reduced the relevance for a precise nomenclature in classifying EVs, therefore leading to a confusing scientific production. The aim of this review was to analyze the evolution of the progress in the knowledge and definition of EVs over the years, with an overview of the methodologies used for the identification of the vesicles, their cell of origin, and the detection of their cargo. The MISEV 2018 guidelines for the proper recognition nomenclature and ways to study EVs are summarized. The review finishes with a “more questions than answers” chapter, in which some of the problems we still face to fully understand the EV function and potential as a diagnostic and therapeutic tool are analyzed. Full article
(This article belongs to the Special Issue Thrombo-Inflammatory Extracellular Vesicles)
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