2022
DOI: 10.3390/biology11040595
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SERPINE1 rs6092 Variant Is Related to Plasma Coagulation Proteins in Patients with Severe COVID-19 from a Tertiary Care Hospital

Abstract: An impaired coagulation process has been described in patients with severe or critical coronavirus disease (COVID-19). Nevertheless, the implication of coagulation-related genes has not been explored. We aimed to evaluate the impact of F5 rs6025 and SERPINE1 rs6092 on invasive mechanical ventilation (IMV) requirement and the levels of coagulation proteins among patients with severe COVID-19. Four-hundred fifty-five patients with severe COVID-19 were genotyped using TaqMan assays. Coagulation-related proteins (… Show more

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Cited by 9 publications
(7 citation statements)
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“…The discovery of PAI-1 targeting CTSL, previously unknown, along with our demonstration of PAI-1's direct inhibition of TMPRSS2 for the first time in this study, implicates the inhibition of both primary (TMPRSS2) and auxiliary (CTSL) proteases in SARS-CoV-2 maturation. Our findings indicate a functional link between extracellular PAI-1 levels and the control of SARS-CoV-2 spread, potentially explaining the underlying mechanism behind other reports linking the presence of the PAI-1 single nucleotide polymorphism rs6092 to increased disease severity in COVID-19 73 . Moreover, the discovery of PAI-1 targeting CTSL may have implications beyond infectious diseases, as this pair has been found to be upregulated concurrently in the metastasis of various cancers [74][75][76] , suggesting a functional rather than merely correlative aspect of disease outcome.…”
Section: Discussionsupporting
confidence: 60%
“…The discovery of PAI-1 targeting CTSL, previously unknown, along with our demonstration of PAI-1's direct inhibition of TMPRSS2 for the first time in this study, implicates the inhibition of both primary (TMPRSS2) and auxiliary (CTSL) proteases in SARS-CoV-2 maturation. Our findings indicate a functional link between extracellular PAI-1 levels and the control of SARS-CoV-2 spread, potentially explaining the underlying mechanism behind other reports linking the presence of the PAI-1 single nucleotide polymorphism rs6092 to increased disease severity in COVID-19 73 . Moreover, the discovery of PAI-1 targeting CTSL may have implications beyond infectious diseases, as this pair has been found to be upregulated concurrently in the metastasis of various cancers [74][75][76] , suggesting a functional rather than merely correlative aspect of disease outcome.…”
Section: Discussionsupporting
confidence: 60%
“…Likewise, fibrinolytic activity may be suppressed due to a rise in PAI-1 levels [ 166. , 167. , 168.…”
Section: Interaction Between Systemic Inflammation and Coagulationmentioning
confidence: 99%
“…According to the results, LINC00659 and UXT antisense RNA 1 (UXT-AS1) were upregulated in DVT patients, possibly because both of these lncRNAs sponge miR-15 and miR-143, which otherwise would inhibit the expression of the pro-thrombotic genes serpin family E member 1 (SERPINE1) and hypoxia-inducible factor 1 subunit alpha (HIF1A). The former encodes for plasminogen activator inhibitor 1 (PAI-1), a key inhibitor of fibrinolysis, by blocking the activation of plasminogen to plasmin [118]. On the other hand, HIF1 (encoded by HIF1A) regulates the activity of the NLR family pyrin domain containing 3 (NLRP3) inflammasome, a protein complex involved in the formation of blood clots under hypoxia [119].…”
Section: Linc00659 and Uxt-as1mentioning
confidence: 99%