Factor XII – What's important but not commonly thought about
Abstract Factor XII (FXII) becomes a serine protease when blood is exposed to artificial medical surfaces or when pathologic surfaces arise in disease states leading to its autoactivation. Initiation of the blood coagulation cascade was the first recognized activity of FXIIa. Blocking FXIIa activity...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-10-01
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| Series: | Research and Practice in Thrombosis and Haemostasis |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/rth2.12235 |
| _version_ | 1797763064979783680 |
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| author | Alvin H. Schmaier Evi X. Stavrou |
| author_facet | Alvin H. Schmaier Evi X. Stavrou |
| author_sort | Alvin H. Schmaier |
| collection | DOAJ |
| description | Abstract Factor XII (FXII) becomes a serine protease when blood is exposed to artificial medical surfaces or when pathologic surfaces arise in disease states leading to its autoactivation. Initiation of the blood coagulation cascade was the first recognized activity of FXIIa. Blocking FXIIa activity formed on artificial medical surfaces should reduce induced blood coagulation leading to thrombosis. In contrast to FXII enzymatic activities, less is known about zymogen FXII functions. Studies show that zymogen FXII has biologic activity in various cells in vivo. In endothelium, FXII stimulates cell growth and proliferation and, in vivo, neoangiogenesis after injury. In fibroblasts, transforming growth factor‐β increases FXII expression, which in turn stimulates fibroblast proliferation, contributing to tissue fibrosis. In neutrophils, FXII stimulates Akt2 to initiate neutrophil adhesion, migration, and chemotaxis, priming events leading to NETosis. Factor FXII deficiency leads to decreased neutrophil recruitment and improved wound healing. In dendritic cells, FXII contributes to neuroinflammation, and its deficiency or pharmacologic inhibition renders mice less susceptible to autoimmune encephalomyelitis. These combined studies indicate that FXII also contributes to multiple components of the inflammatory response. In sum, targeting FXII's biologic activities may provide novel approaches to reduce thrombosis and the inflammatory response in various disease states. |
| first_indexed | 2024-03-12T19:36:14Z |
| format | Article |
| id | doaj.art-2ed883b80004454282d5723961e9aea0 |
| institution | Directory Open Access Journal |
| issn | 2475-0379 |
| language | English |
| last_indexed | 2024-03-12T19:36:14Z |
| publishDate | 2019-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Research and Practice in Thrombosis and Haemostasis |
| spelling | doaj.art-2ed883b80004454282d5723961e9aea02023-08-02T04:07:00ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792019-10-013459960610.1002/rth2.12235Factor XII – What's important but not commonly thought aboutAlvin H. Schmaier0Evi X. Stavrou1Department of Medicine Case Western Reserve University Cleveland OhioDepartment of Medicine Case Western Reserve University Cleveland OhioAbstract Factor XII (FXII) becomes a serine protease when blood is exposed to artificial medical surfaces or when pathologic surfaces arise in disease states leading to its autoactivation. Initiation of the blood coagulation cascade was the first recognized activity of FXIIa. Blocking FXIIa activity formed on artificial medical surfaces should reduce induced blood coagulation leading to thrombosis. In contrast to FXII enzymatic activities, less is known about zymogen FXII functions. Studies show that zymogen FXII has biologic activity in various cells in vivo. In endothelium, FXII stimulates cell growth and proliferation and, in vivo, neoangiogenesis after injury. In fibroblasts, transforming growth factor‐β increases FXII expression, which in turn stimulates fibroblast proliferation, contributing to tissue fibrosis. In neutrophils, FXII stimulates Akt2 to initiate neutrophil adhesion, migration, and chemotaxis, priming events leading to NETosis. Factor FXII deficiency leads to decreased neutrophil recruitment and improved wound healing. In dendritic cells, FXII contributes to neuroinflammation, and its deficiency or pharmacologic inhibition renders mice less susceptible to autoimmune encephalomyelitis. These combined studies indicate that FXII also contributes to multiple components of the inflammatory response. In sum, targeting FXII's biologic activities may provide novel approaches to reduce thrombosis and the inflammatory response in various disease states.https://doi.org/10.1002/rth2.12235C1 inhibitorcontact activationfactor XIIhigh‐molecular‐weight kininogenprekallikreinurokinase plasminogen activator receptor |
| spellingShingle | Alvin H. Schmaier Evi X. Stavrou Factor XII – What's important but not commonly thought about Research and Practice in Thrombosis and Haemostasis C1 inhibitor contact activation factor XII high‐molecular‐weight kininogen prekallikrein urokinase plasminogen activator receptor |
| title | Factor XII – What's important but not commonly thought about |
| title_full | Factor XII – What's important but not commonly thought about |
| title_fullStr | Factor XII – What's important but not commonly thought about |
| title_full_unstemmed | Factor XII – What's important but not commonly thought about |
| title_short | Factor XII – What's important but not commonly thought about |
| title_sort | factor xii what s important but not commonly thought about |
| topic | C1 inhibitor contact activation factor XII high‐molecular‐weight kininogen prekallikrein urokinase plasminogen activator receptor |
| url | https://doi.org/10.1002/rth2.12235 |
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