Abstract
Platelet G-protein-coupled receptors influence platelet function by mediating the response to various agonists, including ADP, thromboxane A2 , and thrombin. Blockade of the ADP receptor, P2Y12 , in combination with cyclooxygenase-1 inhibition by aspirin has been among the most widely used pharmacological strategies to reduce cardiovascular event occurrence in high-risk patients. The latter dual pathway blockade strategy is one of the greatest advances in the field of cardiovascular medicine. In addition to P2Y12 , the platelet thrombin receptor, protease activated receptor-1, has also been recently targeted for inhibition. Blockade of protease activated receptor-1 has been associated with reduced thrombotic event occurrence when added to a strategy using P2Y12 and cyclooxygenase-1 inhibition. At this time, the relative contributions of these G-protein-coupled receptor signaling pathways to in vivo thrombosis remain incompletely defined. The observation of treatment failure in ?10% of high-risk patients treated with aspirin and potent P2Y12 inhibitors provides the rationale for targeting novel pathways mediating platelet function. Targeting intracellular signaling downstream from G-protein-coupled receptor receptors with phosphotidylionisitol 3-kinase and Gq inhibitors are among the novel strategies under investigation to prevent arterial ischemic event occurrence. Greater understanding of the mechanisms of G-protein-coupled receptor-mediated signaling may allow the tailoring of antiplatelet therapy.
Original language | English (US) |
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Pages (from-to) | 500-512 |
Number of pages | 13 |
Journal | Arteriosclerosis, thrombosis, and vascular biology |
Volume | 35 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2015 |
Keywords
- GTP-binding proteins
- blood platelet
- coronary disease
- purinerginc 2Y12 receptor agoists
- receptors
- thrombin
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine