ADPase CD39 Fused to Glycoprotein VI‐Fc Boosts Local Antithrombotic Effects at Vascular Lesions

摘要

BackgroundGPVI (Glycoprotein VI) is the essential platelet collagen receptor in atherothrombosis. Dimeric GPVI‐Fc (Revacept) binds to GPVI binding sites on plaque collagen. As expected, it did not increase bleeding in clinical studies. GPVI‐Fc is a potent inhibitor of atherosclerotic plaque‐induced platelet aggregation at high shear flow, but its inhibition at low shear flow is limited. We sought to increase the platelet inhibitory potential by fusing GPVI‐Fc to the ectonucleotidase CD39 (fusion protein GPVI‐CD39), which inhibits local ADP accumulation at vascular plaques, and thus to create a lesion‐directed dual antiplatelet therapy that is expected to lack systemic bleeding risks.