Tytuł
Cystathionine β-synthase deficiency: different changes in proteomes of thrombosis-resistant Cbs−/− mice and thrombosis-prone CBS−/− humans
Autorzy
[ 1 ] Instytut Chemii Bioorganicznej Polskiej Akademii Nauk, Polska Akademia Nauk | [ P ] pracownik
Dyscyplina naukowa (Ustawa 2.0)
Rok publikacji
2020
Opublikowano w
Typ artykułu
artykuł naukowy
Język publikacji
angielski
Słowa kluczowe
Streszczenie
EN 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.
Strony (od-do)
10726
Typ licencji
CC BY-ND (uznanie autorstwa - bez utworów zależnych)
Wersja tekstu w otwartym dostępie
ostateczna wersja opublikowana
Data udostępnienia
07.2020
Czas udostępnienia publikacji w sposób otwarty
w momencie opublikowania
Punktacja Ministerstwa / czasopismo
140
Punktacja Ministerstwa / czasopismo w ewaluacji 2017-2021
140
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