Endothelial-dependent S-Sulfhydration of tissue factor pathway inhibitor regulates blood coagulation

• DOI: 10.1016/j.redox.2023.102694
• Publication Date: 2023-04-03T15:41:00Z
• Authors: Janina Wittig; Maria-Kyriaki Dre...; Anastasia Kyselova; Fredy Delgado Lagos; Magdalena L. Boch...; Jiong Hu; Katrin Schäfer; Ingrid Fleming; Sofia-Iris Bibli
• Keywords: Endothelial Dysfunction; Thromboplastin

Tissue factor pathway inhibitor (TFPI) is an important regulator of coagulation and a link between inflammation thrombosis. Here we investigated whether endothelial cell-driven oxidative post-translational modifications could have impact on TFPI activity. We focused S-sulfhydration, which hydrogen sulfide-dependent modification that, in cells, regulated by the enzyme cystathionine γ-lyase (CSE). The study made use human primary cells blood from healthy individuals or subjects with atherosclerosis as well mice lacking CSE. was S-sulfhydrated mice, while loss CSE expression/activity reduced its modification. Non-S-sulfhydrated no longer able to interact Xa, facilitated activation tissue factor. Similarly, non-S-sulfhydratable mutants bound less protein S, supplementation sulfide donors, preserved Phenotypically, S-sulfhydration increased clot retraction, suggesting that this new cell-dependent mechanism contributes regulation coagulation.