A serpin with a finger in many PAI’s: PAI-1’s central function in thromboinflammation and cardiovascular disease
Plasminogen activator inhibitor 1 (PAI-1) is a member of the serine protease inhibitor (serpin) superfamily. PAI-1 is the principal inhibitor of the plasminogen activators, tissue plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). Turbulence in the levels of PAI-1 tilts the...
| Hauptverfasser: | , , |
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| Format: | Journal article |
| Sprache: | English |
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Frontiers Media
2021
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| _version_ | 1826268382814535680 |
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| author | Morrow, GB Whyte, C Mutch, N |
| author_facet | Morrow, GB Whyte, C Mutch, N |
| author_sort | Morrow, GB |
| collection | OXFORD |
| description | Plasminogen activator inhibitor 1 (PAI-1) is a member of the serine protease inhibitor (serpin) superfamily. PAI-1 is the principal inhibitor of the plasminogen activators, tissue plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). Turbulence in the levels of PAI-1 tilts the balance of the haemostatic system resulting in bleeding or thrombotic complications. Not surprisingly there is strong evidence that documents the role of PAI-1 in cardiovascular disease. The more recent uncovering of the coalition between the haemostatic and inflammatory pathways have exposed a distinct role for PAI-1. The storm of proinflammatory cytokines liberated during inflammation, including IL-6 and TNFα, directly influence PAI-1 synthesis and increase circulating levels of this serpin. Consequently, elevated levels of PAI-1 are commonplace during infection and are frequently associated with a hypofibrinolytic state and thrombotic complications. Elevated PAI-1 levels are also a feature of metabolic syndrome, which is defined by a cluster of abnormalities including obesity, type 2 diabetes, hypertension and elevated triglyceride. Metabolic syndrome is in itself defined as a proinflammatory state associated with elevated levels of cytokines. In addition, insulin has a direct impact on PAI-1 synthesis bridging these pathways. This review describes the key physiological functions of PAI-1 and how these become perturbed during disease processes. We focus on the direct relationship between PAI-1 and inflammation and the repercussion in terms of an ensuing hypofibrinolytic state and thromboembolic complications. Collectively these observations strengthen the utility of PAI-1 as a viable drug target for treatment of various diseases.
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| first_indexed | 2024-03-06T21:08:50Z |
| format | Journal article |
| id | oxford-uuid:3d6f32e1-16b9-418a-a59c-5cd98c0c261d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:08:50Z |
| publishDate | 2021 |
| publisher | Frontiers Media |
| record_format | dspace |
| spelling | oxford-uuid:3d6f32e1-16b9-418a-a59c-5cd98c0c261d2022-03-26T14:19:21ZA serpin with a finger in many PAI’s: PAI-1’s central function in thromboinflammation and cardiovascular diseaseJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3d6f32e1-16b9-418a-a59c-5cd98c0c261dEnglishSymplectic ElementsFrontiers Media2021Morrow, GBWhyte, CMutch, NPlasminogen activator inhibitor 1 (PAI-1) is a member of the serine protease inhibitor (serpin) superfamily. PAI-1 is the principal inhibitor of the plasminogen activators, tissue plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). Turbulence in the levels of PAI-1 tilts the balance of the haemostatic system resulting in bleeding or thrombotic complications. Not surprisingly there is strong evidence that documents the role of PAI-1 in cardiovascular disease. The more recent uncovering of the coalition between the haemostatic and inflammatory pathways have exposed a distinct role for PAI-1. The storm of proinflammatory cytokines liberated during inflammation, including IL-6 and TNFα, directly influence PAI-1 synthesis and increase circulating levels of this serpin. Consequently, elevated levels of PAI-1 are commonplace during infection and are frequently associated with a hypofibrinolytic state and thrombotic complications. Elevated PAI-1 levels are also a feature of metabolic syndrome, which is defined by a cluster of abnormalities including obesity, type 2 diabetes, hypertension and elevated triglyceride. Metabolic syndrome is in itself defined as a proinflammatory state associated with elevated levels of cytokines. In addition, insulin has a direct impact on PAI-1 synthesis bridging these pathways. This review describes the key physiological functions of PAI-1 and how these become perturbed during disease processes. We focus on the direct relationship between PAI-1 and inflammation and the repercussion in terms of an ensuing hypofibrinolytic state and thromboembolic complications. Collectively these observations strengthen the utility of PAI-1 as a viable drug target for treatment of various diseases. |
| spellingShingle | Morrow, GB Whyte, C Mutch, N A serpin with a finger in many PAI’s: PAI-1’s central function in thromboinflammation and cardiovascular disease |
| title | A serpin with a finger in many PAI’s: PAI-1’s central function in thromboinflammation and cardiovascular disease |
| title_full | A serpin with a finger in many PAI’s: PAI-1’s central function in thromboinflammation and cardiovascular disease |
| title_fullStr | A serpin with a finger in many PAI’s: PAI-1’s central function in thromboinflammation and cardiovascular disease |
| title_full_unstemmed | A serpin with a finger in many PAI’s: PAI-1’s central function in thromboinflammation and cardiovascular disease |
| title_short | A serpin with a finger in many PAI’s: PAI-1’s central function in thromboinflammation and cardiovascular disease |
| title_sort | serpin with a finger in many pai s pai 1 s central function in thromboinflammation and cardiovascular disease |
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