Factor V and thrombotic disease: description of a janus-faced protein.
(2002) In Arteriosclerosis, Thrombosis and Vascular Biology 22(4). p.530-538- Abstract
- The generation of thrombin by the prothrombinase complex constitutes an essential step in hemostasis, with thrombin being crucial for the amplification of blood coagulation, fibrin formation, and platelet activation. In the prothrombinase complex, the activated form of coagulation factor V (FVa) is an essential cofactor to the enzyme-activated factor X (FXa), FXa being virtually ineffective in the absence of its cofactor. Besides its procoagulant potential, intact factor V (FV) has an anticoagulant cofactor capacity functioning in synergy with protein S and activated protein C (APC) in APC-catalyzed inactivation of the activated form of factor VIII. The expression of anticoagulant cofactor function of FV is dependent on APC-mediated... (More)
- The generation of thrombin by the prothrombinase complex constitutes an essential step in hemostasis, with thrombin being crucial for the amplification of blood coagulation, fibrin formation, and platelet activation. In the prothrombinase complex, the activated form of coagulation factor V (FVa) is an essential cofactor to the enzyme-activated factor X (FXa), FXa being virtually ineffective in the absence of its cofactor. Besides its procoagulant potential, intact factor V (FV) has an anticoagulant cofactor capacity functioning in synergy with protein S and activated protein C (APC) in APC-catalyzed inactivation of the activated form of factor VIII. The expression of anticoagulant cofactor function of FV is dependent on APC-mediated proteolysis of intact FV. Thus, FV has the potential to function in procoagulant and anticoagulant pathways, with its functional properties being modulated by proteolysis exerted by procoagulant and anticoagulant enzymes. The procoagulant enzymes factor Xa and thrombin are both able to activate circulating FV to FVa. The activity of FVa is, in turn, regulated by APC together with its cofactor protein S. In fact, the regulation of thrombin formation proceeds primarily through the upregulation and downregulation of FVa cofactor activity, and failure to control FVa activity may result in either bleeding or thrombotic complications. A prime example is APC resistance, which is the most common genetic risk factor for thrombosis. It is caused by a single point mutation in the FV gene (factor V(Leiden)) that not only renders FVa less susceptible to the proteolytic inactivation by APC but also impairs the anticoagulant properties of FV. This review gives a description of the dualistic character of FV and describes the gene-gene and gene-environment interactions that are important for the involvement of FV in the etiology of venous thromboembolism. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/107635
- author
- Nicolaes, Gerry A F and Dahlbäck, Björn LU
- organization
- publishing date
- 2002
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Venous Thrombosis : blood, Thrombin : metabolism, Protein S : physiology, Protein C : physiology, Protein C : genetics, Point Mutation, Phenotype, Activated Protein C Resistance : genetics, Blood Coagulation : physiology, Caucasoid Race, Factor V : biosynthesis, Factor V : genetics, Factor V : metabolism, Factor V : physiology, Factor VIII : genetics, Factor VIII : physiology, Factor Va : physiology, Factor Va : genetics, Factor Xa : metabolism, Factor Xa : physiology, Human, Venous Thrombosis : genetics
- in
- Arteriosclerosis, Thrombosis and Vascular Biology
- volume
- 22
- issue
- 4
- pages
- 530 - 538
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- pmid:11950687
- wos:000175208700004
- scopus:0036124011
- ISSN
- 1524-4636
- DOI
- 10.1161/01.ATV.0000012665.51263.B7
- language
- English
- LU publication?
- yes
- id
- 57f7dc3b-a1e6-4a3c-abe1-e359e3e367c2 (old id 107635)
- alternative location
- http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11950687&dopt=Abstract
- date added to LUP
- 2016-04-01 12:35:37
- date last changed
- 2022-04-13 21:01:03
@article{57f7dc3b-a1e6-4a3c-abe1-e359e3e367c2, abstract = {{The generation of thrombin by the prothrombinase complex constitutes an essential step in hemostasis, with thrombin being crucial for the amplification of blood coagulation, fibrin formation, and platelet activation. In the prothrombinase complex, the activated form of coagulation factor V (FVa) is an essential cofactor to the enzyme-activated factor X (FXa), FXa being virtually ineffective in the absence of its cofactor. Besides its procoagulant potential, intact factor V (FV) has an anticoagulant cofactor capacity functioning in synergy with protein S and activated protein C (APC) in APC-catalyzed inactivation of the activated form of factor VIII. The expression of anticoagulant cofactor function of FV is dependent on APC-mediated proteolysis of intact FV. Thus, FV has the potential to function in procoagulant and anticoagulant pathways, with its functional properties being modulated by proteolysis exerted by procoagulant and anticoagulant enzymes. The procoagulant enzymes factor Xa and thrombin are both able to activate circulating FV to FVa. The activity of FVa is, in turn, regulated by APC together with its cofactor protein S. In fact, the regulation of thrombin formation proceeds primarily through the upregulation and downregulation of FVa cofactor activity, and failure to control FVa activity may result in either bleeding or thrombotic complications. A prime example is APC resistance, which is the most common genetic risk factor for thrombosis. It is caused by a single point mutation in the FV gene (factor V(Leiden)) that not only renders FVa less susceptible to the proteolytic inactivation by APC but also impairs the anticoagulant properties of FV. This review gives a description of the dualistic character of FV and describes the gene-gene and gene-environment interactions that are important for the involvement of FV in the etiology of venous thromboembolism.}}, author = {{Nicolaes, Gerry A F and Dahlbäck, Björn}}, issn = {{1524-4636}}, keywords = {{Venous Thrombosis : blood; Thrombin : metabolism; Protein S : physiology; Protein C : physiology; Protein C : genetics; Point Mutation; Phenotype; Activated Protein C Resistance : genetics; Blood Coagulation : physiology; Caucasoid Race; Factor V : biosynthesis; Factor V : genetics; Factor V : metabolism; Factor V : physiology; Factor VIII : genetics; Factor VIII : physiology; Factor Va : physiology; Factor Va : genetics; Factor Xa : metabolism; Factor Xa : physiology; Human; Venous Thrombosis : genetics}}, language = {{eng}}, number = {{4}}, pages = {{530--538}}, publisher = {{Lippincott Williams & Wilkins}}, series = {{Arteriosclerosis, Thrombosis and Vascular Biology}}, title = {{Factor V and thrombotic disease: description of a janus-faced protein.}}, url = {{http://dx.doi.org/10.1161/01.ATV.0000012665.51263.B7}}, doi = {{10.1161/01.ATV.0000012665.51263.B7}}, volume = {{22}}, year = {{2002}}, }