Proteome and Metabolome\nProfiling of Anticoagulant\nDisorders Induced by Familial Protein S Deficiency

Protein S deficiency\n(PSD) is an autosomal dominant disorder characterized\nby congenital thrombophilia. Studies on PSD are limited yet, resulting\nin a lack of clarity about molecular changes during abnormal coagulation.\nProteomics and metabolomics analyses were conducted on the plasma\nof PSD patients based on liquid and gas chromatography–mass\nspectrometry (LC- and GC–MS). Differential proteins and metabolites\nof PSD were then filtered by univariate statistical analysis and subjected\nto network analysis using the ingenuity pathway analysis (IPA) platform.\nThe proteome and metabolome of PSD were obviously disturbed, and the\nbiological pathway of coagulation and complement cascades was the\nmost affected. During PSD, overall levels of anticoagulant protein\ndecreased and negative regulation of thrombin production was reduced,\ncausing the formation of fibrin clots and platelet aggregation. Furthermore,\n9 differential proteins correlated significantly with protein S, comprising\nA2M, AGT, APOE, FGG, GPLD1, IGHV1–69, CFHR5, CPN2, and CA1.\nThe biological networks suggested that the pathways of acute phase\nresponse, FXR/RXR activation, serotonin receptor signaling, and p70S6K\nsignaling were associated with PSD, indicating an interaction disorder\nof inflammatory immune and lipid metabolism. The findings may contribute\nto knowledge of available functional molecules and biological pathways\nof familial PSD and help with treatment improvement. Data are available\nvia ProteomeXchange with identifier PXD055111 and MetaboLights with\nreference number MTBLS2653.