Investigators from the DZHK partner site Munich have compared two approaches for selectively inhibiting clumping of blood platelets (thrombocytes) in the proximity of ruptured plaques without increasing the risk of bleeding in other parts of the body. The study focuses on glycoprotein VI (GPVI), a receptor found only on thrombocytes. This receptor binds to plaque collagen and is therefore crucially involved in platelet adhesion in regions with ruptured plaques, for instance in the arteries. The investigators inhibited the receptor with the corresponding antibodies. In addition, they produced a protein (the GPVI-Fc fusion protein) which occupies the platelet binding sites in collagen. They were able to show that GPVI antibodies prevented platelet adhesion more effectively than GPVI-Fc. But, surprisingly, inhibition by GPVI-Fc was flow-dependent. This suggests that GPVI-Fc may be suitable for selectively inhibiting platelet clumping at plaques with a high risk for rupture located at sites where the flow rate is high.
The scientists ultimately conclude that the new GPVI inhibitors can counteract blood clots in the arteries more effectively and with fewer side effects that the current standard of treatment with aspirin and so-called P2Y12 antagonists.