SERPINE1 in ARDS: an emerging regulator of inflammation-coagulation-fibrinolysis crosstalk

This narrative review synthesizes current evidence on the role of SERPINE1/PAI-1 in acute respiratory distress syndrome (ARDS), with particular emphasis on inflammation-coagulation-fibrinolysis crosstalk.

Published experimental, translational, genetic, and clinical studies addressing SERPINE1/PAI-1 in ARDS and related critical illnesses were summarized.

Not applicable.

We summarized evidence on the pathobiological functions, cellular sources, biomarker potential, genetic associations, and therapeutic implications of SERPINE1/PAI-1.

SERPINE1 limits tissue-type and urokinase-type plasminogen activator activity, thereby promoting hypofibrinolysis and persistent fibrin deposition in the injured lung. Experimental and clinical evidence further links elevated PAI-1 to inflammatory amplification, endothelial injury, pulmonary microvascular thrombosis, greater disease severity, and adverse outcomes, although the strength of evidence and the degree of causal support vary across these processes. High-expression SERPINE1 variants may also influence clinical outcomes in selected critical illness settings. Pharmacological PAI-1 inhibition is biologically plausible, but its translation to ARDS remains limited by disease heterogeneity, uncertainty regarding treatment timing, and the risk of bleeding.

SERPINE1 is a potentially important integrative regulator and biomarker of dysregulated inflammation, coagulation, and fibrinolysis in ARDS. Future studies should clarify its causal, cell-specific, and phenotype-dependent roles to facilitate the development of targeted therapeutic strategies.