Impaired alpha(IIb)beta(3) integrin activation and shear-dependent thrombus formation in mice lacking phospholipase D1.
Sci Signal
; 3(103): ra1, 2010 Jan 05.
Article
em En
| MEDLINE
| ID: mdl-20051593
ABSTRACT
Platelet aggregation is essential for hemostasis but can also cause myocardial infarction and stroke. A key but poorly understood step in platelet activation is the shift of the principal adhesive receptor, alpha(IIb)beta(3) integrin, from a low- to high-affinity state for its ligands, a process that enables adhesion and aggregation. In response to stimulation of heterotrimeric guanosine triphosphate-binding protein or immunoreceptor tyrosine-based activation motif-coupled receptors, phospholipases cleave membrane phospholipids to generate lipid and soluble second messengers. An essential role in platelet activation has been established for phospholipase C (PLC) but not for PLD and its product phosphatidic acid. Here, we report that platelets from Pld1(-/-) mice displayed impaired alpha(IIb)beta(3) integrin activation in response to major agonists and defective glycoprotein Ib-dependent aggregate formation under high shear conditions. These defects resulted in protection from thrombosis and ischemic brain infarction without affecting tail bleeding times. These results indicate that PLD1 may be a critical regulator of platelet activity in the setting of ischemic cardiovascular and cerebrovascular events.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fosfolipase D
/
Trombose
/
Plaquetas
/
Agregação Plaquetária
/
Complexo Glicoproteico GPIIb-IIIa de Plaquetas
/
Infarto Encefálico
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article