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10.3390/v13112209

http://scihub22266oqcxt.onion/10.3390/v13112209
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suck abstract from ncbi


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pmid34835015      Viruses 2021 ; 13 (11): ä
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  • SARS-CoV-2 Spike Protein S1-Mediated Endothelial Injury and Pro-Inflammatory State Is Amplified by Dihydrotestosterone and Prevented by Mineralocorticoid Antagonism #MMPMID34835015
  • Kumar N; Zuo Y; Yalavarthi S; Hunker KL; Knight JS; Kanthi Y; Obi AT; Ganesh SK
  • Viruses 2021[Nov]; 13 (11): ä PMID34835015show ga
  • Men are disproportionately affected by the coronavirus disease-2019 (COVID-19), and face higher odds of severe illness and death compared to women. The vascular effects of androgen signaling and inflammatory cytokines in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-mediated endothelial injury are not defined. We determined the effects of SARS-CoV-2 spike protein-mediated endothelial injury under conditions of exposure to androgen dihydrotestosterone (DHT) and tumor necrosis factor-a (TNF-alpha) and tested potentially therapeutic effects of mineralocorticoid receptor antagonism by spironolactone. Circulating endothelial injury markers VCAM-1 and E-selectin were measured in men and women diagnosed with COVID-19. Exposure of endothelial cells (ECs) in vitro to DHT exacerbated spike protein S1-mediated endothelial injury transcripts for the cell adhesion molecules E-selectin, VCAM-1 and ICAM-1 and anti-fibrinolytic PAI-1 (p < 0.05), and increased THP-1 monocyte adhesion to ECs (p = 0.032). Spironolactone dramatically reduced DHT+S1-induced endothelial activation. TNF-alpha exacerbated S1-induced EC activation, which was abrogated by pretreatment with spironolactone. Analysis from patients hospitalized with COVID-19 showed concordant higher circulating VCAM-1 and E-Selectin levels in men, compared to women. A beneficial effect of the FDA-approved drug spironolactone was observed on endothelial cells in vitro, supporting a rationale for further evaluation of mineralocorticoid antagonism as an adjunct treatment in COVID-19.
  • |*Inflammation[MESH]
  • |Angiotensin Receptor Antagonists/pharmacology[MESH]
  • |COVID-19/*pathology/physiopathology/virology[MESH]
  • |Cell Adhesion Molecules/blood[MESH]
  • |Cells, Cultured[MESH]
  • |Dihydrotestosterone/*pharmacology[MESH]
  • |Endothelium, Vascular/drug effects/metabolism/*pathology[MESH]
  • |Female[MESH]
  • |Humans[MESH]
  • |Male[MESH]
  • |SARS-CoV-2/*physiology[MESH]
  • |Sex Characteristics[MESH]
  • |Spike Glycoprotein, Coronavirus/*physiology[MESH]
  • |Spironolactone/*pharmacology[MESH]
  • |Tumor Necrosis Factor-alpha/pharmacology/physiology[MESH]


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