Background: Vascular endothelial cells activation and dysfunction mediate inflammation and abnormal coagulation in COVID-19 patients. Mineralocorticoid receptor (MR) signaling and its downstream target Galectin-3 (Gal-3) are known to mediate cardiovascular inflammation and might be involved in the pathogenesis of COVID-19 complications. Accordingly, we aimed to investigate the potential beneficial effects of MR antagonism and Gal-3 inhibition on the inflammatory response induced by SARS-CoV-2 Spike protein in human aortic endothelial cells (HAECs). Methods: HAECs were treated with recombinant SARS-COV2 Spike (S) protein. MR antagonists (namely spironolactone and eplerenone) or the Gal-3 inhibitor G3P-01 were supplemented before and after S protein challenge. HAECs supernatants were assessed by ELISA or Western blotting. Results: HAECs treated with recombinant S protein resulted in enhanced secretion of inflammatory molecules (interleukin-6, monocyte chemoattractant protein-1, interleukin-18, interleukin-27, and interferon-γ) as well as in the thrombosis marker plasminogen activator inhibitor (PAI)-1. This was prevented and reversed by both MR antagonists and G3P-01. Conclusions: These findings indicate that MR/Gal-3 pathway blockade could be a promising option to reduce endothelial inflammation in SARS-CoV-2 infection.
【저자키워드】 Inflammation, SARS-CoV2, spike, mineralocorticoid receptor, endothelial cells, 【초록키워드】 SARS-CoV-2, thrombosis, S protein, SARS-COV-2 infection, interleukin-6, ELISA, Protein, pathway, galectin-3, complications, receptor, inhibitor, COVID-19 patients, marker, Endothelial cell, Signaling, Inflammatory response, Inflammatory, dysfunction, interferon-γ, endothelial, monocyte chemoattractant protein-1, Activation, abnormal coagulation, secretion, pathogenesis of COVID-19, blockade, western blotting, supernatant, downstream, antagonist, Effect, involved, treated, reduce, prevented, reversed, recombinant S protein, Mineralocorticoid, were assessed, 【제목키워드】 SARS-CoV-2, induced, Effect,