Gap Junctions between Endothelial Cells Are Disrupted by Circulating Extracellular Vesicles from Sickle Cell Patients with Acute Chest Syndrome

Intercellular junctions maintain the integrity of the endothelium. We previously found that the adherens and tight junctions between endothelial cells are disrupted by plasma extracellular vesicles from patients with sickle cell disease (especially those with Acute Chest Syndrome). In the current st...

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Main Authors: Joanna Gemel, Yifan Mao, Gabrielle Lapping-Carr, Eric C. Beyer
Format: Article
Language:English
Published: MDPI AG 2020-11-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/21/23/8884
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author Joanna Gemel
Yifan Mao
Gabrielle Lapping-Carr
Eric C. Beyer
author_facet Joanna Gemel
Yifan Mao
Gabrielle Lapping-Carr
Eric C. Beyer
author_sort Joanna Gemel
collection DOAJ
description Intercellular junctions maintain the integrity of the endothelium. We previously found that the adherens and tight junctions between endothelial cells are disrupted by plasma extracellular vesicles from patients with sickle cell disease (especially those with Acute Chest Syndrome). In the current study, we evaluated the effects of these vesicles on endothelial gap junctions. The vesicles from sickle cell patients (isolated during episodes of Acute Chest Syndrome) disrupted gap junction structures earlier and more severely than the other classes of intercellular junctions (as detected by immunofluorescence). These vesicles were much more potent than those isolated at baseline from the same subject. The treatment of endothelial cells with these vesicles led to reduced levels of connexin43 mRNA and protein. These vesicles severely reduced intercellular communication (transfer of microinjected Neurobiotin). Our data suggest a hierarchy of progressive disruption of different intercellular connections between endothelial cells by circulating extracellular vesicles that may contribute to the pathophysiology of the endothelial disturbances in sickle cell disease.
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spelling doaj.art-ba37f70a253f471d9487cf19fd85b2e22023-11-20T22:04:17ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-11-012123888410.3390/ijms21238884Gap Junctions between Endothelial Cells Are Disrupted by Circulating Extracellular Vesicles from Sickle Cell Patients with Acute Chest SyndromeJoanna Gemel0Yifan Mao1Gabrielle Lapping-Carr2Eric C. Beyer3Department of Pediatrics, University of Chicago, Chicago, IL 60637, USADepartment of Pediatrics, University of Chicago, Chicago, IL 60637, USADepartment of Pediatrics, University of Chicago, Chicago, IL 60637, USADepartment of Pediatrics, University of Chicago, Chicago, IL 60637, USAIntercellular junctions maintain the integrity of the endothelium. We previously found that the adherens and tight junctions between endothelial cells are disrupted by plasma extracellular vesicles from patients with sickle cell disease (especially those with Acute Chest Syndrome). In the current study, we evaluated the effects of these vesicles on endothelial gap junctions. The vesicles from sickle cell patients (isolated during episodes of Acute Chest Syndrome) disrupted gap junction structures earlier and more severely than the other classes of intercellular junctions (as detected by immunofluorescence). These vesicles were much more potent than those isolated at baseline from the same subject. The treatment of endothelial cells with these vesicles led to reduced levels of connexin43 mRNA and protein. These vesicles severely reduced intercellular communication (transfer of microinjected Neurobiotin). Our data suggest a hierarchy of progressive disruption of different intercellular connections between endothelial cells by circulating extracellular vesicles that may contribute to the pathophysiology of the endothelial disturbances in sickle cell disease.https://www.mdpi.com/1422-0067/21/23/8884Connexin43endotheliumgap junctionsickle cell diseasetight junctionextracellular vesicle
spellingShingle Joanna Gemel
Yifan Mao
Gabrielle Lapping-Carr
Eric C. Beyer
Gap Junctions between Endothelial Cells Are Disrupted by Circulating Extracellular Vesicles from Sickle Cell Patients with Acute Chest Syndrome
International Journal of Molecular Sciences
Connexin43
endothelium
gap junction
sickle cell disease
tight junction
extracellular vesicle
title Gap Junctions between Endothelial Cells Are Disrupted by Circulating Extracellular Vesicles from Sickle Cell Patients with Acute Chest Syndrome
title_full Gap Junctions between Endothelial Cells Are Disrupted by Circulating Extracellular Vesicles from Sickle Cell Patients with Acute Chest Syndrome
title_fullStr Gap Junctions between Endothelial Cells Are Disrupted by Circulating Extracellular Vesicles from Sickle Cell Patients with Acute Chest Syndrome
title_full_unstemmed Gap Junctions between Endothelial Cells Are Disrupted by Circulating Extracellular Vesicles from Sickle Cell Patients with Acute Chest Syndrome
title_short Gap Junctions between Endothelial Cells Are Disrupted by Circulating Extracellular Vesicles from Sickle Cell Patients with Acute Chest Syndrome
title_sort gap junctions between endothelial cells are disrupted by circulating extracellular vesicles from sickle cell patients with acute chest syndrome
topic Connexin43
endothelium
gap junction
sickle cell disease
tight junction
extracellular vesicle
url https://www.mdpi.com/1422-0067/21/23/8884
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