Glycoprotein VI in securing vascular integrity in inflamed vessels

Abstract

Essentials Platelets can stop bleeding independently of integrin-mediated aggregation in inflamed organs. GPVI contributes to aggregation-independent hemostasis in the inflamed skin. GPVI supports sealing of neutrophil-induced vascular breaches by nonaggregated platelets. Evaluation of anti-GPVI drugs should take into account the risk of inflammatory bleeding. Glycoprotein VI (GPVI), the main platelet receptor for collagen, has been shown to play a central role in various models of thrombosis, and to be a minor actor of hemostasis at sites of trauma. These observations have made of GPVI a novel target for antithrombotic therapy, as its inhibition would ideally combine efficacy with safety. Nevertheless, recent studies have indicated that GPVI could play an important role in preventing bleeding caused by neutrophils in the inflamed skin and lungs. Remarkably, there is evidence that the GPVI-dependent hemostatic function of platelets at the acute phase of inflammation in these organs does not involve aggregation. From a therapeutic perspective, the vasculoprotective action of GPVI in inflammation suggests that blocking of GPVI might bear some risks of bleeding at sites of neutrophil infiltration. In this review, we summarize recent findings on GPVI functions in inflammation and discuss their possible clinical implications and applications.