| Autor: |
Tetiana Yatsenko, Rios, Ricardo, Nogueira, Tatiane, Salama, Yousef, Takahashi, Satoshi, Adachi, Eisuke, Yoko Tabe, Nobutaka Hattori, Taro Osada, Toshio Naito, Kazuhisa Takahashi, Koichi Hattori, Beate Heissig |
| Předmět: |
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| Zdroj: |
Frontiers in Immunology; 2024, p1-17, 17p |
| Abstrakt: |
Introduction: Plasminogen activator inhibitor-1 (PAI-1) is linked to thrombosis and endothelial dysfunction in severe COVID-19. The +43 G>A PAI-1 and 4G/5G promoter polymorphism can influence PAI-1 expression. The 4G5G PAI-1 promoter gene polymorphism constitutes the 4G4G, 4G5G, and 5G5G genotypes. However, the impact of PAI-1 polymorphisms on disease severity or endothelial dysfunction remains unclear. Methods: Clinical data, sera, and peripheral blood mononuclear cells (PBMCs) of COVID-19 patients were studied. Results: Comorbidities and clinical biomarkers did not correlate with genotypes in either polymorphism. However, differences between fibrinolytic factors and interleukin-1b (IL-1b) were identified in genotypes of the 4G/5G but not the 43 G>A PAI polymorphism. Patients with the 4G4G genotype of the 4G/5G polymorphism showed high circulating PAI-1, mainly complexed with plasminogen activators, and low IL-1b and plasmin levels, indicating suppressed fibrinolysis. NFkB was upregulated in PBMCs of COVID-19 patients with the 4G4G genotype. Discussion: Mechanistically, IL-1b enhanced PAI-1 expression in 4G4G endothelial cells, preventing the generation of plasmin and cleavage products like angiostatin, soluble uPAR, and VCAM1. We identified inflammation-induced endothelial dysfunction coupled with fibrinolytic system overactivation as a risk factor for patients with the 5G5G genotype. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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