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• W3038735634 abstract "Abstract Cystathionine β-synthase (CBS)-deficient patients are prone to vascular thrombosis. In contrast, Cbs −/− mice show no abnormalities in blood coagulation. To identify molecular basis underlying these disparately different thrombotic phenotypes, we analyzed plasma proteomes of Cbs −/− vs. Cbs +/+ mice (8-month-old, 12/group, sex-matched) and CBS −/− vs. CBS +/+ humans (37 ± 7-year-old, 10–14/group, sex-matched) using label-free mass spectrometry. We identified 117 and 41 differentiating plasma proteins in Cbs −/− mice and CBS −/− humans, respectively. Twenty-one proteins were shared between CBS −/− humans and Cbs −/− mice, with sixteen changed in the opposite direction. Proteins involved in blood coagulation and complement/coagulation cascades represented a greater fraction of the differentiating proteins in CBS −/− patients (51%) than in Cbs −/− mice (21%). Top canonical pathways, identified by Ingenuity Pathways Analysis, such as LXR/RXR, FXR/RXR activation (− log[ P -value] = 30–31) and atherosclerosis signaling (− log[ P -value] = 10–11) were similarly affected in Cbs −/− mice and CBS −/− humans. The Coagulation System was affected stronger in CBS −/− humans than in Cbs −/− mice (− log[ P -value] = 15 vs. 10, respectively) while acute phase response and complement system were affected stronger in Cbs −/− mice (− log[ P -value] = 33 and 22, respectively) than in humans (− log[ P -value] = 22 and 6, respectively). Other pathways, including IL-7 signaling and B cell development were affected only in Cbs −/− mice. Taken together, our findings suggest that differences in these processes, in particular in the Coagulation System, could account for the thrombotic phenotype in CBS −/− patients and the absence of thrombosis in Cbs −/− mice. Overall, our findings suggest that Cbs −/− mice have a better adaptive response to protect from prothrombotic effects of hyperhomocysteinemia than CBS −/− humans." @default.
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• W3038735634 date "2020-07-01" @default.
• W3038735634 modified "2023-09-26" @default.
• W3038735634 title "Cystathionine β-synthase deficiency: different changes in proteomes of thrombosis-resistant Cbs−/− mice and thrombosis-prone CBS−/− humans" @default.
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• W3038735634 doi "https://doi.org/10.1038/s41598-020-67672-5" @default.
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