title: Protein disulfide-isomerase - a trigger of tissue factor-dependent thrombosis.
abstract: The plasmatic coagulation system is tightly controlled by natural anticoagulant mechanisms, preventing thrombosis to ensure the supply of tissues with oxygen and nutrients without provoking susceptibility to bleeding diatheses. The membrane receptor tissue factor (TF) is the principal initiator of coagulation, forming a high affinity complex with coagulation factor VIIa, thus catalyzing quantitative formation of the coagulation factor Xa. While it has been well-established that the TF-VIIa complex is efficiently blocked by factor Xa associated with tissue factor pathway inhibitor (TFPI), it was uncovered during the last decade that TF contains an intramolecular allosteric disulfide, which is prone to reduction and is crucial for TF's procoagulant and prothrombotic function. The compromised integrity of the allosteric TF disulfide pair Cys186/Cys209 was demonstrated to be responsible for the cryptic nature of TF procoagulant activity on monocytes and other cell types as well as in mouse thrombosis models. Cell surface associated protein disulfide-isomerases (PDI) were identified as activators of cryptic tissue factor. Here, we review this current concept of TF de-encryption by PDI oxidoreductases that have become interesting targets for the development of new antithrombotic treatment strategies.
authors.forename: Klytaimnistra
authors.initials: K
authors.lastname: Kiouptsi
authors.forename: Christoph
authors.initials: C
authors.lastname: Reinhardt
mesh_terms: D001777:Blood Coagulation / Q000502:physiology*; D015942:Factor VIIa; D006801:Humans; D019704:Protein Disulfide-Isomerases / Q000378:metabolism*; D013927:Thrombosis / Q000097:blood*
chemical_list: D015942:Factor VIIa; D019704:Protein Disulfide-Isomerases
keywords: PDI; Thrombosis; protein disulfide-isomerase; tissue factor