| First Author | Sikora M | Year | 2020 |
| Journal | Sci Rep | Volume | 10 |
| Issue | 1 | Pages | 10726 |
| PubMed ID | 32612202 | Mgi Jnum | J:294188 |
| Mgi Id | MGI:6453196 | Doi | 10.1038/s41598-020-67672-5 |
| Citation | Sikora M, et al. (2020) Cystathionine beta-synthase deficiency: different changes in proteomes of thrombosis-resistant Cbs(-/-) mice and thrombosis-prone CBS(-/-) humans. Sci Rep 10(1):10726 |
| abstractText | Cystathionine beta-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. |
