Dataset Information

Hydrogen Sulfide Ameliorates SARS-CoV-2-Associated Lung Endothelial Barrier Disruption.

ABSTRACT: Recent studies have confirmed that lung microvascular endothelial injury plays a critical role in the pathophysiology of COVID-19. Our group and others have demonstrated the beneficial effects of H₂S in several pathological processes and provided a rationale for considering the therapeutic implications of H₂S in COVID-19 therapy. Here, we evaluated the effect of the slow-releasing H₂S donor, GYY4137, on the barrier function of a lung endothelial cell monolayer in vitro, after challenging the cells with plasma samples from COVID-19 patients or inactivated SARS-CoV-2 virus. We also assessed how the cytokine/chemokine profile of patients' plasma, endothelial barrier permeability, and disease severity correlated with each other. Alterations in barrier permeability after treatments with patient plasma, inactivated virus, and GYY4137 were monitored and assessed by electrical impedance measurements in real time. We present evidence that GYY4137 treatment reduced endothelial barrier permeability after plasma challenge and completely reversed the endothelial barrier disruption caused by inactivated SARS-CoV-2 virus. We also showed that disease severity correlated with the cytokine/chemokine profile of the plasma but not with barrier permeability changes in our assay. Overall, these data demonstrate that treatment with H₂S-releasing compounds has the potential to ameliorate SARS-CoV-2-associated lung endothelial barrier disruption.

SUBMITTER: Escaffre O

PROVIDER: S-EPMC10376201 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hydrogen Sulfide Ameliorates SARS-CoV-2-Associated Lung Endothelial Barrier Disruption.

Escaffre Olivier O Szaniszlo Peter P Törő Gabor G Vilas Caitlyn L CL Servantes Brenna J BJ Lopez Ernesto E Juelich Terry L TL Levine Corri B CB McLellan Susan L F SLF Cardenas Jessica C JC Freiberg Alexander N AN Módis Katalin K

Biomedicines 20230622 7

Recent studies have confirmed that lung microvascular endothelial injury plays a critical role in the pathophysiology of COVID-19. Our group and others have demonstrated the beneficial effects of H2S in several pathological processes and provided a rationale for considering the therapeutic implications of H2S in COVID-19 therapy. Here, we evaluated the effect of the slow-releasing H2S donor, GYY4137, on the barrier function of a lung endothelial cell monolayer in ...[more]

PMID: 37509430

Similar Datasets

Project description:Vascular permeability is a hallmark of acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury pathobiology; however, the mechanisms underlying this vascular dysregulation remain unclear, thereby impairing the development of desperately needed effective therapeutics. We have shown that sphingosine-1-phosphate (S1P) and 2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol (FTY720) analogues are useful tools for exploring vascular barrier regulation mechanisms. To experimentally define the effects of FTY720 regioisomers on lung endothelial cell barrier regulation. Specific barrier-regulatory receptor and kinase inhibitors were utilized to probe signaling mechanisms involved in FTY720 regioisomer-mediated human lung endothelial cell barrier responses (trans-endothelial electrical resistance, TER). Docking simulations with the S1P1 receptor were performed to further evaluate FTY720 regioisomer signaling. FTY720 regioisomers produced potent endothelial cell barrier disruption reflected by declines in TER alterations. Pharmacologic inhibition of Gi-coupled S1P receptors (S1P1, S1P2, S1P3) failed to alter FTY720 regioisomer-mediated barrier disruption; findings that were corroborated by docking simulations demonstrating FTY720 regiosomers were repelled from S1P1 docking, in contrast to strong S1P1 binding elicited by S1P. Inhibition of either the barrier-disrupting PAR-1 receptor, the VEGF receptor, Rho-kinase, MAPK, NFkB, or PI3K failed to alter FTY720 regioisomer-induced endothelial cell barrier disruption. While FTY720 regioisomers significantly increased protein phosphatase 2 (PP2A) activity, PP2A inhibitors failed to alter FTY720 regioisomer-induced endothelial cell barrier disruption. Together, these results imply a vexing model of pulmonary vascular barrier dysregulation in response to FTY720-related compounds and highlight the need for further insights into mechanisms of vascular integrity required to promote the development of novel therapeutic tools to prevent or reverse the pulmonary vascular leak central to ARDS outcomes.

Dataset Information

Hydrogen Sulfide Ameliorates SARS-CoV-2-Associated Lung Endothelial Barrier Disruption.

Publications

Hydrogen Sulfide Ameliorates SARS-CoV-2-Associated Lung Endothelial Barrier Disruption.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets