期刊
BIOMEDICINES
卷 9, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/biomedicines9060639
关键词
SARS-CoV2; Spike; endothelial cells; inflammation; mineralocorticoid receptor
资金
- Instituto de Salud Carlos III-FEDER [CP13/00221]
- G3 Pharmaceuticals
- FIGHT-HF [ANR-15-RHU-0004]
- MIRCOV grant
- Instituto de Salud Carlos III [FI19/00302, CD19/00251]
The study found that using MR antagonists and Gal-3 inhibitors effectively blocked the inflammatory response and thrombosis induced by SARS-CoV-2 Spike protein, reducing the risk of complications in COVID-19 patients.
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-gamma) 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.
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