Journal
FRONTIERS IN CARDIOVASCULAR MEDICINE
Volume 9, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcvm.2022.878199
Keywords
anticoagulants; coagulation factors; hemostasis; serine protease inhibitors; thrombosis
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Appropriate activation of coagulation requires a balance between procoagulant and anticoagulant proteins in blood. SERPIN anticoagulants function by forming irreversible inhibitory complexes with target coagulation proteases. Mutations in SERPIN family members can cause hereditary thrombophilias, and low plasma levels of SERPINs are associated with an increased risk of thrombosis. Engineered SERPINs hold potential as novel therapies for the treatment of thrombotic pathologies.
Appropriate activation of coagulation requires a balance between procoagulant and anticoagulant proteins in blood. Loss in this balance leads to hemorrhage and thrombosis. A number of endogenous anticoagulant proteins, such as antithrombin and heparin cofactor II, are members of the serine protease inhibitor (SERPIN) family. These SERPIN anticoagulants function by forming irreversible inhibitory complexes with target coagulation proteases. Mutations in SERPIN family members, such as antithrombin, can cause hereditary thrombophilias. In addition, low plasma levels of SERPINs have been associated with an increased risk of thrombosis. Here, we review the biological activities of the different anticoagulant SERPINs. We further consider the clinical consequences of SERPIN deficiencies and insights gained from preclinical disease models. Finally, we discuss the potential utility of engineered SERPINs as novel therapies for the treatment of thrombotic pathologies.
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