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Thrombo-Inflammatory Extracellular Vesicles 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 14002

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Guest Editor
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
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Special Issue Information

Dear Colleagues,

The term “extracellular vesicles” (EVs) 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 EVs 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 EVs 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
Guest Editor

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Keywords

  • extracellular vesicles
  • inflammation
  • thrombosis
  • airway diseases
  • cardiovascular diseases
  • biomarkers
  • EV mechanisms of action

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Published Papers (7 papers)

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Editorial

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2 pages, 173 KiB  
Editorial
Thrombo-Inflammatory Extracellular Vesicles 2.0
by Tommaso Neri
Int. J. Mol. Sci. 2023, 24(22), 16134; https://doi.org/10.3390/ijms242216134 - 9 Nov 2023
Viewed by 625
Abstract
In the complex field of cell-to-cell communication and physiological regulation, there is a remarkable category of tiny messengers called extracellular vesicles (EVs) [...] Full article
(This article belongs to the Special Issue Thrombo-Inflammatory Extracellular Vesicles 2.0)

Research

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24 pages, 11174 KiB  
Article
Shear-Mediated Platelet Microparticles Demonstrate Phenotypic Heterogeneity as to Morphology, Receptor Distribution, and Hemostatic Function
by Yana Roka-Moiia, Kaitlyn R. Ammann, Samuel Miller-Gutierrez, Jawaad Sheriff, Danny Bluestein, Joseph E. Italiano, Robert C. Flaumenhaft and Marvin J. Slepian
Int. J. Mol. Sci. 2023, 24(8), 7386; https://doi.org/10.3390/ijms24087386 - 17 Apr 2023
Cited by 2 | Viewed by 2085
Abstract
Implantable Cardiovascular Therapeutic Devices (CTD), while lifesaving, impart supraphysiologic shear stress to platelets, resulting in thrombotic and bleeding coagulopathy. We previously demonstrated that shear-mediated platelet dysfunction is associated with downregulation of platelet GPIb-IX-V and αIIbβ3 receptors via generation of Platelet-Derived MicroParticles (PDMPs). Here, [...] Read more.
Implantable Cardiovascular Therapeutic Devices (CTD), while lifesaving, impart supraphysiologic shear stress to platelets, resulting in thrombotic and bleeding coagulopathy. We previously demonstrated that shear-mediated platelet dysfunction is associated with downregulation of platelet GPIb-IX-V and αIIbβ3 receptors via generation of Platelet-Derived MicroParticles (PDMPs). Here, we test the hypothesis that sheared PDMPs manifest phenotypical heterogeneity of morphology and receptor surface expression and modulate platelet hemostatic function. Human gel-filtered platelets were exposed to continuous shear stress. Alterations of platelet morphology were visualized using transmission electron microscopy. Surface expression of platelet receptors and PDMP generation were quantified by flow cytometry. Thrombin generation was quantified spectrophotometrically, and platelet aggregation was measured by optical aggregometry. Shear stress promotes notable alterations in platelet morphology and ejection of distinctive types of PDMPs. Shear-mediated microvesiculation is associated with the remodeling of platelet receptors, with PDMPs expressing significantly higher levels of adhesion receptors (αIIbβ3, GPIX, PECAM-1, P-selectin, and PSGL-1) and agonist receptors (P2Y12 and PAR1). Sheared PDMPs promote thrombin generation and inhibit platelet aggregation induced by collagen and ADP. Sheared PDMPs demonstrate phenotypic heterogeneity as to morphology and defined patterns of surface receptors and impose a bidirectional effect on platelet hemostatic function. PDMP heterogeneity suggests that a range of mechanisms are operative in the microvesiculation process, contributing to CTD coagulopathy and posing opportunities for therapeutic manipulation. Full article
(This article belongs to the Special Issue Thrombo-Inflammatory Extracellular Vesicles 2.0)
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11 pages, 2005 KiB  
Article
Do Circulating Extracellular Vesicles Strictly Reflect Bronchoalveolar Lavage Extracellular Vesicles in COPD?
by Mariaenrica Tinè, Tommaso Neri, Davide Biondini, Nicol Bernardinello, Alvise Casara, Maria Conti, Marianna Minniti, Manuel G. Cosio, Marina Saetta, Alessandro Celi, Dario Nieri and Erica Bazzan
Int. J. Mol. Sci. 2023, 24(3), 2966; https://doi.org/10.3390/ijms24032966 - 3 Feb 2023
Cited by 4 | Viewed by 1505
Abstract
Cell-derived extracellular vesicles (EVs) found in the circulation and body fluids contain biomolecules that could be used as biomarkers for lung and other diseases. EVs from bronchoalveolar lavage (BAL) might be more informative of lung abnormalities than EVs from blood, where information might [...] Read more.
Cell-derived extracellular vesicles (EVs) found in the circulation and body fluids contain biomolecules that could be used as biomarkers for lung and other diseases. EVs from bronchoalveolar lavage (BAL) might be more informative of lung abnormalities than EVs from blood, where information might be diluted. To compare EVs’ characteristics in BAL and blood in smokers with and without COPD. Same-day BAL and blood samples were obtained in 9 nonsmokers (NS), 11 smokers w/o COPD (S), and 9 with COPD (SCOPD) (FEV1: 59 ± 3% pred). After differential centrifugation, EVs (200–500 nm diameter) were identified by flow cytometry and labeled with cell-type specific antigens: CD14 for macrophage-derived EVs, CD326 for epithelial-derived EVs, CD146 for endothelial-derived EVs, and CD62E for activated-endothelial-derived EVs. In BAL, CD14-EVs were increased in S compared to NS [384 (56–567) vs. 172 (115–282) events/μL; p = 0.007] and further increased in SCOPD [619 (224–888)] compared to both S (p = 0.04) and NS (p < 0.001). CD326-EVs were increased in S [760 (48–2856) events/μL, p < 0.001] and in SCOPD [1055 (194–11,491), p < 0.001] when compared to NS [15 (0–68)]. CD146-EVs and CD62E-EVs were similar in the three groups. In BAL, significant differences in macrophage and epithelial-derived EVs can be clearly detected between NS, S and SCOPD, while these differences were not found in plasma. This suggests that BAL is a better medium than blood to study EVs in lung diseases. Full article
(This article belongs to the Special Issue Thrombo-Inflammatory Extracellular Vesicles 2.0)
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17 pages, 3546 KiB  
Article
Extracellular Vesicles Released after Doxorubicin Treatment in Rats Protect Cardiomyocytes from Oxidative Damage and Induce Pro-Inflammatory Gene Expression in Macrophages
by Chontida Yarana, Panjaree Siwaponanan, Chayodom Maneechote, Thawatchai Khuanjing, Benjamin Ongnok, Nanthip Prathumsap, Siriporn C. Chattipakorn, Nipon Chattipakorn and Kovit Pattanapanyasat
Int. J. Mol. Sci. 2022, 23(21), 13465; https://doi.org/10.3390/ijms232113465 - 3 Nov 2022
Cited by 3 | Viewed by 2081
Abstract
Doxorubicin (DOXO)-induced cardiomyopathy (DIC) is a lethal complication in cancer patients. Major mechanisms of DIC involve oxidative stress in cardiomyocytes and hyperactivated immune response. Extracellular vesicles (EVs) mediate cell–cell communication during oxidative stress. However, functions of circulating EVs released after chronic DOXO exposure [...] Read more.
Doxorubicin (DOXO)-induced cardiomyopathy (DIC) is a lethal complication in cancer patients. Major mechanisms of DIC involve oxidative stress in cardiomyocytes and hyperactivated immune response. Extracellular vesicles (EVs) mediate cell–cell communication during oxidative stress. However, functions of circulating EVs released after chronic DOXO exposure on cardiomyocytes and immune cells are still obscured. Herein, we developed a DIC in vivo model using male Wistar rats injected with 3 mg/kg DOXO for 6 doses within 30 days (18 mg/kg cumulative dose). One month after the last injection, the rats developed cardiotoxicity evidenced by increased BCL2-associated X protein and cleaved caspase-3 in heart tissues, along with N-terminal pro B-type natriuretic peptide in sera. Serum EVs were isolated by size exclusion chromatography. EV functions on H9c2 cardiomyocytes and NR8383 macrophages were evaluated. EVs from DOXO-treated rats (DOXO_EVs) attenuated ROS production via increased glutathione peroxidase-1 and catalase gene expression, and reduced hydrogen peroxide-induced cell death in cardiomyocytes. In contrast, DOXO_EVs induced ROS production, interleukin-6, and tumor necrosis factor-alpha, while suppressing arginase-1 gene expression in macrophages. These results suggested the pleiotropic roles of EVs against DIC, which highlight the potential role of EV-based therapy for DIC with a concern of its adverse effect on immune response. Full article
(This article belongs to the Special Issue Thrombo-Inflammatory Extracellular Vesicles 2.0)
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Review

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18 pages, 881 KiB  
Review
Extracellular Vesicles (EVs) as Crucial Mediators of Cell-Cell Interaction in Asthma
by Mariaenrica Tinè, Ylenia Padrin, Matteo Bonato, Umberto Semenzato, Erica Bazzan, Maria Conti, Marina Saetta, Graziella Turato and Simonetta Baraldo
Int. J. Mol. Sci. 2023, 24(5), 4645; https://doi.org/10.3390/ijms24054645 - 28 Feb 2023
Viewed by 1998
Abstract
Asthma is the most common chronic respiratory disorder worldwide and accounts for a huge health and economic burden. Its incidence is rapidly increasing but, in parallel, novel personalized approaches have emerged. Indeed, the improved knowledge of cells and molecules mediating asthma pathogenesis has [...] Read more.
Asthma is the most common chronic respiratory disorder worldwide and accounts for a huge health and economic burden. Its incidence is rapidly increasing but, in parallel, novel personalized approaches have emerged. Indeed, the improved knowledge of cells and molecules mediating asthma pathogenesis has led to the development of targeted therapies that significantly increased our ability to treat asthma patients, especially in severe stages of disease. In such complex scenarios, extracellular vesicles (EVs i.e., anucleated particles transporting nucleic acids, cytokines, and lipids) have gained the spotlight, being considered key sensors and mediators of the mechanisms controlling cell-to-cell interplay. We will herein first revise the existing evidence, mainly by mechanistic studies in vitro and in animal models, that EV content and release is strongly influenced by the specific triggers of asthma. Current studies indicate that EVs are released by potentially all cell subtypes in the asthmatic airways, particularly by bronchial epithelial cells (with different cargoes in the apical and basolateral side) and inflammatory cells. Such studies largely suggest a pro-inflammatory and pro-remodelling role of EVs, whereas a minority of reports indicate protective effects, particularly by mesenchymal cells. The co-existence of several confounding factors—including technical pitfalls and host and environmental confounders—is still a major challenge in human studies. Technical standardization in isolating EVs from different body fluids and careful selection of patients will provide the basis for obtaining reliable results and extend their application as effective biomarkers in asthma. Full article
(This article belongs to the Special Issue Thrombo-Inflammatory Extracellular Vesicles 2.0)
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16 pages, 583 KiB  
Review
Extracellular Vesicles: New Players in the Mechanisms of Sepsis- and COVID-19-Related Thromboinflammation
by Martina Schiavello, Barbara Vizio, Ornella Bosco, Emanuele Pivetta, Filippo Mariano, Giuseppe Montrucchio and Enrico Lupia
Int. J. Mol. Sci. 2023, 24(3), 1920; https://doi.org/10.3390/ijms24031920 - 18 Jan 2023
Cited by 4 | Viewed by 2680
Abstract
Sepsis and COVID-19 patients often manifest an imbalance in inflammation and coagulation, a complex pathological mechanism also named thromboinflammation, which strongly affects patient prognosis. Extracellular vesicles (EVs) are nanoparticles released by cells into extracellular space that have a relevant role in cell-to-cell communication. [...] Read more.
Sepsis and COVID-19 patients often manifest an imbalance in inflammation and coagulation, a complex pathological mechanism also named thromboinflammation, which strongly affects patient prognosis. Extracellular vesicles (EVs) are nanoparticles released by cells into extracellular space that have a relevant role in cell-to-cell communication. Recently, EVs have been shown to act as important players in a variety of pathologies, including cancer and cardiovascular disease. The biological properties of EVs in the mechanisms of thromboinflammation during sepsis and COVID-19 are still only partially known. Herein, we summarize the current experimental evidence on the role of EVs in thromboinflammation, both in bacterial sepsis and in COVID-19. A better understanding of EV involvement in these processes could be useful in describing novel diagnostic and therapeutic applications of EVs in these diseases. Full article
(This article belongs to the Special Issue Thrombo-Inflammatory Extracellular Vesicles 2.0)
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13 pages, 1509 KiB  
Review
Extracellular Vesicles in Atrial Fibrillation—State of the Art
by Grzegorz Procyk, Dominik Bilicki, Paweł Balsam, Piotr Lodziński, Marcin Grabowski and Aleksandra Gąsecka
Int. J. Mol. Sci. 2022, 23(14), 7591; https://doi.org/10.3390/ijms23147591 - 8 Jul 2022
Cited by 6 | Viewed by 2416
Abstract
Extracellular vesicles are particles released from cells and delimited by a lipid bilayer. They have been widely studied, including extensive investigation in cardiovascular diseases. Many scientists have explored their role in atrial fibrillation. Patients suffering from atrial fibrillation have been evidenced to present [...] Read more.
Extracellular vesicles are particles released from cells and delimited by a lipid bilayer. They have been widely studied, including extensive investigation in cardiovascular diseases. Many scientists have explored their role in atrial fibrillation. Patients suffering from atrial fibrillation have been evidenced to present altered levels of these particles as well as changed amounts of their contents such as micro-ribonucleic acids (miRs). Although many observations have been made so far, a large randomized clinical trial is needed to assess the previous findings. This review aims to thoroughly summarize current research regarding extracellular vesicles in atrial fibrillation. Full article
(This article belongs to the Special Issue Thrombo-Inflammatory Extracellular Vesicles 2.0)
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