G protein-coupled receptor kinase 5 regulates thrombin signaling in platelets.
mutation
platelet
pulmonary
thrombosis
Journal
Research and practice in thrombosis and haemostasis
ISSN: 2475-0379
Titre abrégé: Res Pract Thromb Haemost
Pays: United States
ID NLM: 101703775
Informations de publication
Date de publication:
Aug 2024
Aug 2024
Historique:
received:
17
04
2024
revised:
28
06
2024
accepted:
16
08
2024
medline:
23
9
2024
pubmed:
23
9
2024
entrez:
23
9
2024
Statut:
epublish
Résumé
Our prior genome-wide association study of thrombin-induced platelet aggregation identified a G protein-coupled receptor kinase 5 (GRK5) noncoding variant (rs10886430-G) that is strongly associated with increased platelet reactivity to thrombin. This variant predisposes to increased risk of stroke, pulmonary embolism, and venous thromboembolism. To determine role of platelet specific GRK5 in platelet responses to agonists and injury. Platelets from GRK5 mutant mice have been shown to have increased thrombin sensitivity, indicating that GRK5 may be a negative regulator of platelet activation. However, this has not been studied in a platelet-specific manner. We therefore used platelet-specific GRK5 mutant mice and models of thrombosis and pulmonary embolism. We now demonstrate that mice lacking GRK5 specifically in platelets had a mild increase in thrombin responses These data indicate that platelet GRK5 has a significant role in limiting platelet responses to thrombin.
Sections du résumé
Background
UNASSIGNED
Our prior genome-wide association study of thrombin-induced platelet aggregation identified a G protein-coupled receptor kinase 5 (GRK5) noncoding variant (rs10886430-G) that is strongly associated with increased platelet reactivity to thrombin. This variant predisposes to increased risk of stroke, pulmonary embolism, and venous thromboembolism.
Objectives
UNASSIGNED
To determine role of platelet specific GRK5 in platelet responses to agonists and injury.
Methods
UNASSIGNED
Platelets from GRK5 mutant mice have been shown to have increased thrombin sensitivity, indicating that GRK5 may be a negative regulator of platelet activation. However, this has not been studied in a platelet-specific manner. We therefore used platelet-specific GRK5 mutant mice and models of thrombosis and pulmonary embolism.
Results
UNASSIGNED
We now demonstrate that mice lacking GRK5 specifically in platelets had a mild increase in thrombin responses
Conclusion
UNASSIGNED
These data indicate that platelet GRK5 has a significant role in limiting platelet responses to thrombin.
Identifiants
pubmed: 39309233
doi: 10.1016/j.rpth.2024.102556
pii: S2475-0379(24)00251-6
pmc: PMC11415800
doi:
Types de publication
Journal Article
Langues
eng
Pagination
102556Informations de copyright
© 2024 The Author(s).