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

• Published in: International journal of molecular sciences Vol. 21; no. 23; p. 8884
• Main Authors: Gemel, Joanna, Mao, Yifan, Lapping-Carr, Gabrielle, Beyer, Eric C.
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24.11.2020; MDPI
• Subjects: Acute Chest Syndrome - complications; Acute Chest Syndrome - genetics; Acute Chest Syndrome - pathology; Adolescent; Adult; Anemia, Sickle Cell - complications; Anemia, Sickle Cell - genetics; Anemia, Sickle Cell - pathology; Animals; Cell Communication - genetics; Child; Child, Preschool; Connexin 43 - genetics; Endothelial Cells - metabolism; Endothelium - metabolism; Endothelium - pathology; Extracellular vesicles; Extracellular Vesicles - genetics; Female; Gap Junctions - genetics; Hemoglobin; Humans; Intercellular Junctions - genetics; Lipids; Male; Membranes; MicroRNAs; Nanoparticles; Plasma; Proteins; Young Adult; endothelium; endothelial integrity; Connexin43; gap junction; extracellular vesicle; tight junction; sickle cell disease
• DOI: 10.3390/ijms21238884
• ISSN: 1422-0067; 1661-6596

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.