Document Type
Article
Publication Date
3-2022
Publication Title
Frontiers in Physiology
Pages
812199 (1-9 pp.)
DOI
10.3389/fphys.2022.812199
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused more than 5 million deaths worldwide. Multiple reports indicate that the endothelium is involved during SARS-Cov-2-related disease (COVID-19). Indeed, COVID-19 patients display increased thrombophilia with arterial and venous embolism and lung microcapillary thrombotic disease as major determinants of deaths. The pathophysiology of endothelial dysfunction in COVID-19 is not completely understood. We have investigated the role of subunit 1 of the SARS-CoV-2 spike protein (S1SP) in eliciting endothelial barrier dysfunction, characterized dose and time relationships, and tested the hypothesis that heat shock protein 90 (HSP90) inhibitors would prevent and repair such injury. S1SP activated (phosphorylated) IKBα, STAT3, and AKT and reduced the expression of intercellular junctional proteins, occludin, and VE-cadherin. HSP90 inhibitors (AT13387 and AUY-922) prevented endothelial barrier dysfunction and hyperpermeability and reduced IKBα and AKT activation. These two inhibitors also blocked S1SP-mediated barrier dysfunction and loss of VE-cadherin. These data suggest that spike protein subunit 1 can elicit, by itself, direct injury to the endothelium and suggest a role of HSP90 inhibitors in preserving endothelial functionality.
Original Publication Citation
Colunga Biancatelli, R.M.L., Solopov, P.A., Gregory, B., Khodour, Y. and Catravas, J.D. (2022). HSP90 inhibitors modulate SARS-CoV-2 spike protein subunit 1-induced human pulmonary microvascular endothelial activation and barrier dysfunction. Frontiers in Physiology 13, Article 812199. https://www.frontiersin.org/article/10.3389/fphys.2022.812199
Repository Citation
Colunga Biancatelli, Ruben Manuel Luciano; Solopov, Pavel; Gregory, Betsy W.; Khodour, Yara; and Catravas, John D., "HSP90 Inhibitors Modulate SARS-CoV-2 Spike Protein Subunit 1-Induced Human Pulmonary Microvascular Endothelial Activation and Barrier Dysfunction" (2022). Bioelectrics Publications. 329.
https://digitalcommons.odu.edu/bioelectrics_pubs/329
ORCID
0000-0002-1174-3876 (Colunga Biancatelli), 0000-0002-1705-027X (Solopov), 0000-0002-5098-295X (Catravas)
Included in
Amino Acids, Peptides, and Proteins Commons, Biomedical Commons, Physiology Commons, Pulmonology Commons, Respiratory System Commons
Comments
Copyright © 2022 Colunga Biancatelli, Solopov, Gregory, Khodour and Catravas. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.