Proteome and Metabolome Profiling of Anticoagulant Disorders Induced by Familial Protein S Deficiency

Protein S deficiency
(PSD) is an autosomal dominant disorder characterized
by congenital thrombophilia. Studies on PSD are limited yet, resulting
in a lack of clarity about molecular changes during abnormal coagulation.
Proteomics and metabolomics analyses were conducted on the plasma
of PSD patients based on liquid and gas chromatography–mass
spectrometry (LC- and GC–MS). Differential proteins and metabolites
of PSD were then filtered by univariate statistical analysis and subjected
to network analysis using the ingenuity pathway analysis (IPA) platform.
The proteome and metabolome of PSD were obviously disturbed, and the
biological pathway of coagulation and complement cascades was the
most affected. During PSD, overall levels of anticoagulant protein
decreased and negative regulation of thrombin production was reduced,
causing the formation of fibrin clots and platelet aggregation. Furthermore,
9 differential proteins correlated significantly with protein S, comprising
A2M, AGT, APOE, FGG, GPLD1, IGHV1–69, CFHR5, CPN2, and CA1.
The biological networks suggested that the pathways of acute phase
response, FXR/RXR activation, serotonin receptor signaling, and p70S6K
signaling were associated with PSD, indicating an interaction disorder
of inflammatory immune and lipid metabolism. The findings may contribute
to knowledge of available functional molecules and biological pathways
of familial PSD and help with treatment improvement. Data are available
via ProteomeXchange with identifier PXD055111 and MetaboLights with
reference number MTBLS2653.