Abstract
BackgroundPlatelets are essential to physiological hemostasis or pathological thrombus formation. Current antiplatelet agents inhibit platelet aggregation but leave patients at risk of systemic side-effects such as hemorrhage. Newer therapeutic strategies could involve targeting this cascade earlier during platelet adhesion or activation via inhibitory effects on specific glycoproteins, the thrombogenic collagen receptors found on the platelet surface.AimsGlycoprotein VI (GPVI) is increasingly being recognized as the main platelet-collagen receptor involved in arterial thrombosis. This review summarizes the crucial role GPVI plays in ischemic stroke as well as the current strategies used to attempt to inhibit its activity.Summary of reviewIn this review, we discuss the normal hemostatic process, and the role GPVI plays at sites of atherosclerotic plaque rupture. We discuss how the unique structure of GPVI allows for its interaction with collagen and creates downstream signaling that leads to thrombus formation. We summarize the current strategies used to inhibit GPVI activity and how this could translate to a clinically viable entity that may compete with current antiplatelet therapy.ConclusionFrom animal models, it is clear that GPVI inhibition leads to an abolished platelet response to collagen and reduced platelet aggregation, culminating in smaller arterial thrombi. There is now an increasing body of evidence that these findings can be translated into the development of a bleeding free pharmacological entity specific to sites of plaque rupture in humans.
Highlights
Ischemic stroke is a worldwide leading cause of disability and death.[1]
We summarize the current strategies used to inhibit Glycoprotein VI (GPVI) activity and how this could translate to a clinically viable entity that may compete with current antiplatelet therapy
From animal models, it is clear that GPVI inhibition leads to an abolished platelet response to collagen and reduced platelet aggregation, culminating in smaller arterial thrombi
Summary
The platelet–collagen interaction, and subsequent platelet activation and thrombus formation, can lead to devastating neurological damage via ischemic stroke. There is a growing body of evidence pointing towards the importance of platelet glycoprotein receptors in stroke due to their requisite role in initiating downstream signaling mechanisms leading to platelet activation and pathological thrombus generation. Current understanding of thrombus formation suggests that GPVI is one such crucial receptor and inhibition of its collagen-induced signaling would be a specific pharmacological target for ischemic stroke. Smaller studies are being carried out looking at novel small molecule inhibitors of GPVI and if a successful entity is discovered, the decade should see the development of efficacious and highly specific therapies in ischemic stroke that a have large safety margin
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