Fibrinogen and Antifibrinolytic Proteins: Interactions and Future Therapeutics

Thrombus formation remains a major cause of morbidity and mortality worldwide. Current antiplatelet and anticoagulant therapies have been effective at reducing vascular events, but at the expense of increased bleeding risk. Targeting proteins that interact with fibrinogen and which are involved in h...

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Autores principales:	Nikoletta Pechlivani, Katherine J. Kearney, Ramzi A. Ajjan
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	fibrinogen antifibrinolytic proteins therapeutics thrombosis bleeding Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/c5f8993cc94b4c139b14d62d406d83c6
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spelling	oai:doaj.org-article:c5f8993cc94b4c139b14d62d406d83c62021-11-25T17:57:36ZFibrinogen and Antifibrinolytic Proteins: Interactions and Future Therapeutics10.3390/ijms2222125371422-00671661-6596https://doaj.org/article/c5f8993cc94b4c139b14d62d406d83c62021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12537https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Thrombus formation remains a major cause of morbidity and mortality worldwide. Current antiplatelet and anticoagulant therapies have been effective at reducing vascular events, but at the expense of increased bleeding risk. Targeting proteins that interact with fibrinogen and which are involved in hypofibrinolysis represents a more specific approach for the development of effective and safe therapeutic agents. The antifibrinolytic proteins alpha-2 antiplasmin (α2AP), thrombin activatable fibrinolysis inhibitor (TAFI), complement C3 and plasminogen activator inhibitor-2 (PAI-2), can be incorporated into the fibrin clot by FXIIIa and affect fibrinolysis by different mechanisms. Therefore, these antifibrinolytic proteins are attractive targets for the development of novel therapeutics, both for the modulation of thrombosis risk, but also for potentially improving clot instability in bleeding disorders. This review summarises the main properties of fibrinogen-bound antifibrinolytic proteins, their effect on clot lysis and association with thrombotic or bleeding conditions. The role of these proteins in therapeutic strategies targeting the fibrinolytic system for thrombotic diseases or bleeding disorders is also discussed.Nikoletta PechlivaniKatherine J. KearneyRamzi A. AjjanMDPI AGarticlefibrinogenantifibrinolytic proteinstherapeuticsthrombosisbleedingBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12537, p 12537 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	fibrinogen antifibrinolytic proteins therapeutics thrombosis bleeding Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	fibrinogen antifibrinolytic proteins therapeutics thrombosis bleeding Biology (General) QH301-705.5 Chemistry QD1-999 Nikoletta Pechlivani Katherine J. Kearney Ramzi A. Ajjan Fibrinogen and Antifibrinolytic Proteins: Interactions and Future Therapeutics
description	Thrombus formation remains a major cause of morbidity and mortality worldwide. Current antiplatelet and anticoagulant therapies have been effective at reducing vascular events, but at the expense of increased bleeding risk. Targeting proteins that interact with fibrinogen and which are involved in hypofibrinolysis represents a more specific approach for the development of effective and safe therapeutic agents. The antifibrinolytic proteins alpha-2 antiplasmin (α2AP), thrombin activatable fibrinolysis inhibitor (TAFI), complement C3 and plasminogen activator inhibitor-2 (PAI-2), can be incorporated into the fibrin clot by FXIIIa and affect fibrinolysis by different mechanisms. Therefore, these antifibrinolytic proteins are attractive targets for the development of novel therapeutics, both for the modulation of thrombosis risk, but also for potentially improving clot instability in bleeding disorders. This review summarises the main properties of fibrinogen-bound antifibrinolytic proteins, their effect on clot lysis and association with thrombotic or bleeding conditions. The role of these proteins in therapeutic strategies targeting the fibrinolytic system for thrombotic diseases or bleeding disorders is also discussed.
format	article
author	Nikoletta Pechlivani Katherine J. Kearney Ramzi A. Ajjan
author_facet	Nikoletta Pechlivani Katherine J. Kearney Ramzi A. Ajjan
author_sort	Nikoletta Pechlivani
title	Fibrinogen and Antifibrinolytic Proteins: Interactions and Future Therapeutics
title_short	Fibrinogen and Antifibrinolytic Proteins: Interactions and Future Therapeutics
title_full	Fibrinogen and Antifibrinolytic Proteins: Interactions and Future Therapeutics
title_fullStr	Fibrinogen and Antifibrinolytic Proteins: Interactions and Future Therapeutics
title_full_unstemmed	Fibrinogen and Antifibrinolytic Proteins: Interactions and Future Therapeutics
title_sort	fibrinogen and antifibrinolytic proteins: interactions and future therapeutics
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c5f8993cc94b4c139b14d62d406d83c6
work_keys_str_mv	AT nikolettapechlivani fibrinogenandantifibrinolyticproteinsinteractionsandfuturetherapeutics AT katherinejkearney fibrinogenandantifibrinolyticproteinsinteractionsandfuturetherapeutics AT ramziaajjan fibrinogenandantifibrinolyticproteinsinteractionsandfuturetherapeutics
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Fibrinogen and Antifibrinolytic Proteins: Interactions and Future Therapeutics

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