Dysregulated lipid metabolites GML and GMO were associated with cytotoxic T cell function and serve as biomarkers for acute pulmonary embolism

Objective To identify serum lipid biomarkers for acute pulmonary embolism (APE) and evaluate their diagnostic value, and to investigate the impact of glycerol monolaurate (GML) and glycerol monooleate (GMO) on cytotoxic T cell function. Methods A total of 436 subjects, including APE, healthy controls, and patients with related diseases, were enrolled. Serum samples were subjected to pseudotargeted lipidomics to screen differential lipid species. Targeted LC-MS/MS analysis was used to validate the GML and GMO levels. Flow cytometry was used to assess cytotoxic T cell markers such as granzyme B, perforin, and granulysin. In vitro experiments examined the inhibitory effect of GML and GMO on Notch1 signaling and cytotoxic protein expression in T cells. ROC curve analyses were performed to evaluate the diagnostic performance of lipid biomarkers. Results Pseudotargeted lipidomics identified 203 upregulated and 57 downregulated serum lipids in APE versus controls. Targeted LC-MS/MS confirmed significantly elevated serum GML and GMO in APE compared with healthy controls and other diseases. Serum GML and GMO were correlated with clinical risk stratification. ROC analyses showed high sensitivity and specificity for GML and GMO individually. Cytotoxic T cells from APE patients exhibited decreased granzyme B, perforin and granulysin. In vitro , GML and GMO reduced Notch1 and granzyme B expression in T cells. Conclusion Elevated serum GML and GMO could serve as effective diagnostic biomarkers for APE, correlating with disease severity. They were likely to impair cytotoxic T cell function by downregulating Notch1 signaling and cytotoxic proteins, suggesting their involvement in APE pathogenesis.