Anticoagulant SERPINs: Endogenous Regulators of Hemostasis and Thrombosis
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...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Cardiovascular Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.878199/full |
| _version_ | 1818160652985827328 |
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| author | Steven P. Grover Nigel Mackman |
| author_facet | Steven P. Grover Nigel Mackman |
| author_sort | Steven P. Grover |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T16:05:17Z |
| format | Article |
| id | doaj.art-0a3cd870983d4d11935e03d6530660bb |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-11T16:05:17Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-0a3cd870983d4d11935e03d6530660bb2022-12-22T00:59:13ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-05-01910.3389/fcvm.2022.878199878199Anticoagulant SERPINs: Endogenous Regulators of Hemostasis and ThrombosisSteven P. GroverNigel MackmanAppropriate 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.https://www.frontiersin.org/articles/10.3389/fcvm.2022.878199/fullanticoagulantscoagulation factorshemostasisserine protease inhibitorsthrombosis |
| spellingShingle | Steven P. Grover Nigel Mackman Anticoagulant SERPINs: Endogenous Regulators of Hemostasis and Thrombosis Frontiers in Cardiovascular Medicine anticoagulants coagulation factors hemostasis serine protease inhibitors thrombosis |
| title | Anticoagulant SERPINs: Endogenous Regulators of Hemostasis and Thrombosis |
| title_full | Anticoagulant SERPINs: Endogenous Regulators of Hemostasis and Thrombosis |
| title_fullStr | Anticoagulant SERPINs: Endogenous Regulators of Hemostasis and Thrombosis |
| title_full_unstemmed | Anticoagulant SERPINs: Endogenous Regulators of Hemostasis and Thrombosis |
| title_short | Anticoagulant SERPINs: Endogenous Regulators of Hemostasis and Thrombosis |
| title_sort | anticoagulant serpins endogenous regulators of hemostasis and thrombosis |
| topic | anticoagulants coagulation factors hemostasis serine protease inhibitors thrombosis |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.878199/full |
| work_keys_str_mv | AT stevenpgrover anticoagulantserpinsendogenousregulatorsofhemostasisandthrombosis AT nigelmackman anticoagulantserpinsendogenousregulatorsofhemostasisandthrombosis |