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Hsp90 Inhibitors Modulate Sars-Cov-2 Spike Protein Subunit 1-Induced Human Pulmonary Microvascular Endothelial Activation And Barrier Dysfunction, Ruben Manuel Luciano Colunga Biancatelli, Pavel Solopov, Betsy W. Gregory, Yara Khodour, John D. Catravas
Hsp90 Inhibitors Modulate Sars-Cov-2 Spike Protein Subunit 1-Induced Human Pulmonary Microvascular Endothelial Activation And Barrier Dysfunction, Ruben Manuel Luciano Colunga Biancatelli, Pavel Solopov, Betsy W. Gregory, Yara Khodour, John D. Catravas
Bioelectrics Publications
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 …
The Heat Shock Protein 90 Inhibitor, At13387, Protects The Alveolo-Capillary Barrier And Prevents Hci-Induced Chronic Lung Injury And Pulmonary Fibrosis, Ruben M.L. Colunga Biancatelli, Pavel Solopov, Christiana Dimitropoulou, Betsy Gregory, Tierney Day, John D. Catravas
The Heat Shock Protein 90 Inhibitor, At13387, Protects The Alveolo-Capillary Barrier And Prevents Hci-Induced Chronic Lung Injury And Pulmonary Fibrosis, Ruben M.L. Colunga Biancatelli, Pavel Solopov, Christiana Dimitropoulou, Betsy Gregory, Tierney Day, John D. Catravas
Bioelectrics Publications
Hydrochloric acid (HCl) exposure causes asthma-like conditions, reactive airways dysfunction syndrome, and pulmonary fibrosis. Heat Shock Protein 90 (HSP90) is a molecular chaperone that regulates multiple cellular processes. HSP90 inhibitors are undergoing clinical trials for cancer and are also being studied in various pre-clinical settings for their anti-inflammatory and anti-fibrotic effects. Here we investigated the ability of the heat shock protein 90 (HSP90) inhibitor AT13387 to prevent chronic lung injury induced by exposure to HCl in vivo and its protective role in the endothelial barrier in vitro. We instilled C57Bl/6J mice with 0.1N HCl (2 µL/g body weight, intratracheally) and …
The Hsp90 Inhibitor, Auy-922, Ameliorates The Development Of Nitrogen Mustard-Induced Pulmonary Fibrosis And Lung Dysfunction In Mice, Pavel Solopov, Ruben M.L. Colunga Biancatelli, Margarita Marinova, Christiana Dimitropoulou, John D. Catravas
The Hsp90 Inhibitor, Auy-922, Ameliorates The Development Of Nitrogen Mustard-Induced Pulmonary Fibrosis And Lung Dysfunction In Mice, Pavel Solopov, Ruben M.L. Colunga Biancatelli, Margarita Marinova, Christiana Dimitropoulou, John D. Catravas
Bioelectrics Publications
Increased levels of heat shock protein 90 (HSP90) have been recently implicated in the pathogenesis of pulmonary fibrosis and the use of HSP90 inhibitors constitutes a potential therapeutic approach. Similarly, acute exposure to nitrogen mustard (NM) is related to the development of chronic lung injury driven by TNF-α, TGF-β, ERK and HSP90. Thus, we developed a murine model of NM-induced pulmonary fibrosis by instilling C57BI/6J mice with 0.625 mg/kg mechlorethamine hydrochloride. After 24 h, mice began receiving AUY-922, a second generation HSP90 inhibitor, at 1 mg/kg 2 times per week or 2 mg/kg 3 times per week, for either 10 …