SERPINE1 in ARDS: an emerging regulator of inflammation-coagulation-fibrinolysis crosstalk.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing mechanistic, preclinical, and observational clinical literature without systematic review methodology
PubMed 42470461 · doi:10.1007/s00011-026-02310-w
What was done
Narrative review synthesizing published experimental, translational, genetic, and clinical studies examining the biological functions, cellular sources, biomarker utility, genetic variants, and therapeutic relevance of SERPINE1 (PAI-1) in acute respiratory distress syndrome (ARDS) and related critical illnesses.
What was found
The abstract reports no numerical data or effect sizes. It qualitatively describes that SERPINE1 inhibits tissue-type and urokinase-type plasminogen activators, leading to hypofibrinolysis and persistent fibrin deposition in the lung. Elevated PAI-1 is linked to inflammation amplification, endothelial injury, pulmonary microvascular thrombosis, increased disease severity, and adverse outcomes. High-expression SERPINE1 genetic variants are also associated with worse clinical outcomes in selected critical illness settings. Pharmacological inhibition remains clinically limited by bleeding risk, uncertain treatment timing, and ARDS heterogeneity.
Why it matters
This review highlights SERPINE1 as a central molecular link across inflammation, coagulation, and fibrinolysis pathways in ARDS. It outlines its potential utility as a biomarker while delineating major translational barriers to targeted anti-PAI-1 therapies.
Limits
The abstract reports no quantitative metrics or systematic literature search criteria. Evidence relies largely on mechanistic, animal, and observational studies with variable causal support, and clinical translation is hindered by bleeding risks and biological heterogeneity across ARDS phenotypes.
Cited by
- contradicts Adipose tissue is the primary source of plasminogen activator inhibitor-1 (PAI-1) in the body.