Role of Factor XIa and Plasma Kallikrein in Arterial and Venous Thrombosis.
Animals
Arterial Occlusive Diseases
/ blood
Blood Coagulation
/ physiology
Blood Coagulation Disorders
/ blood
Blood Coagulation Factors
/ physiology
Disease Models, Animal
Enzyme Activation
Factor XI Deficiency
/ blood
Factor XIa
/ chemistry
Factor Xa Inhibitors
/ therapeutic use
Humans
Mice
Mice, Knockout
Plasma Kallikrein
/ physiology
Prekallikrein
/ deficiency
Protein Processing, Post-Translational
Species Specificity
Thrombophilia
/ drug therapy
Thrombosis
/ blood
Venous Thrombosis
/ blood
Journal
Thrombosis and haemostasis
ISSN: 2567-689X
Titre abrégé: Thromb Haemost
Pays: Germany
ID NLM: 7608063
Informations de publication
Date de publication:
Jun 2020
Jun 2020
Historique:
pubmed:
7
5
2020
medline:
13
7
2021
entrez:
7
5
2020
Statut:
ppublish
Résumé
Cardiovascular disease, including stroke, myocardial infarction, and venous thromboembolism, is one of the leading causes of morbidity and mortality worldwide. Excessive coagulation may cause vascular occlusion in arteries and veins eventually leading to thrombotic diseases. Studies in recent years suggest that coagulation factors are involved in these pathological mechanisms. Factors XIa (FXIa), XIIa (FXIIa), and plasma kallikrein (PKa) of the contact system of coagulation appear to contribute to thrombosis while playing a limited role in hemostasis. Contact activation is initiated upon autoactivation of FXII on negatively charged surfaces. FXIIa activates plasma prekallikrein (PK) to PKa, which in turn activates FXII and initiates the kallikrein-kinin pathway. FXI is also activated by FXIIa, leading to activation of FIX and finally to thrombin formation, which in turn activates FXI in an amplification loop. Animal studies have shown that arterial and venous thrombosis can be reduced by the inhibition of FXI(a) or PKa. Furthermore, data from human studies suggest that these enzymes may be valuable targets to reduce thrombosis risk. In this review, we discuss the structure and function of FXI(a) and PK(a), their involvement in the development of venous and arterial thrombosis in animal models and human studies, and current therapeutic strategies.
Identifiants
pubmed: 32375196
doi: 10.1055/s-0040-1710013
doi:
Substances chimiques
Blood Coagulation Factors
0
Factor Xa Inhibitors
0
Prekallikrein
9055-02-1
Factor XIa
EC 3.4.21.27
Plasma Kallikrein
EC 3.4.21.34
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
883-993Informations de copyright
Georg Thieme Verlag KG Stuttgart · New York.
Déclaration de conflit d'intérêts
S.H. is an employee of Bayer AG, Germany. M.V., H.T.C. and H.M.H.S. have nothing to disclose. H.T.C. was a fellow of the Gutenberg Research Foundation and is adjunct professor at the Center for Thrombosis and Hemostasis, Gutenberg University, Mainz, Germany. H.M.H.S. and H.T.C. receive support from the Netherlands Heart Foundation: CVON2014-09, reappraisal of atrial fibrillation: interaction between hypercoagulability, electrical remodeling, and vascular destabilization in the progression of atrial fibrillation (RACE V).