Hydrogen Sulfide Ameliorates SARS-CoV-2-Associated Lung Endothelial Barrier Disruption.
Olivier EscaffrePeter SzaniszloGabor TörőCaitlyn L VilasBrenna J ServantesErnesto LopezTerry L JuelichCorri B LevineSusan L F McLellanJessica C CardenasAlexander N FreibergKatalin MódisPublished in: Biomedicines (2023)
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 H 2 S in several pathological processes and provided a rationale for considering the therapeutic implications of H 2 S in COVID-19 therapy. Here, we evaluated the effect of the slow-releasing H 2 S 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 H 2 S-releasing compounds has the potential to ameliorate SARS-CoV-2-associated lung endothelial barrier disruption.
Keyphrases
- sars cov
- endothelial cells
- respiratory syndrome coronavirus
- coronavirus disease
- vascular endothelial growth factor
- ejection fraction
- machine learning
- induced apoptosis
- clinical trial
- mouse model
- magnetic resonance imaging
- risk assessment
- high throughput
- case report
- signaling pathway
- bone marrow
- mesenchymal stem cells
- cell proliferation
- replacement therapy
- patient reported outcomes
- endoplasmic reticulum stress
- electronic health record
- climate change
- patient reported