Platelet activation induces a shift toward GPVI dimerization, which correlates with P-selectin exposure in patients with coronary artery disease and is limited by P2Y12 antagonists.
GPVI dimerization is an active process that induces receptor competence and may serve as a new marker to analyze platelet reactivity in coronary artery disease.
OBJECTIVE: The immune receptor homologue glycoprotein VI (GPVI)/FcR receptor γ chain complex is primarily responsible for platelet activation by collagen. There is growing evidence that optimal binding of GPVI to collagen depends on the assembly of GPVI dimers. The valence of GPVI on resting platelets needs to be clearly established because platelet avidity for collagen would be greater if GPVI is constitutively expressed as a dimer than as a monomer. METHODS AND RESULTS: Using a monoclonal antibody (9E18) that preferentially binds to GPVI dimers, we found that GPVI was maintained in a monomeric form on human resting platelets under the control of intraplatelet cAMP concentration. Activation by soluble agonists or von Willebrand factor induced a shift toward GPVI dimerization related to increased platelet adhesion to collagen. A correlation between platelet binding of 9E18 and P-selectin exposure was observed in patients experiencing coronary artery disease, and antagonists of the ADP receptor P2Y12 limited ADP-induced GPVI dimerization. CONCLUSION: The rapid assembly of highly competent dimers of GPVI at sites of vascular lesion represents an important step in the sequence of events leading to platelet activation by collagen. GPVI dimers could represent a new marker to analyze platelet reactivity.
Loyau et al. (Fri,) conducted a other in Coronary artery disease. Platelet activation was evaluated on GPVI dimerization and platelet adhesion to collagen. Platelet activation induces a shift toward GPVI dimerization, which correlates with P-selectin exposure in patients with coronary artery disease and is limited by P2Y12 antagonists.