Anti-Platelet Peptides Targeting αIIbß3 Outside-In Signaling Pathway.

ABSTRACT

Platelets and their progenitors express high levels of integrin αIIbß3, which plays a key role in platelet functions, hemostasis, and arterial thrombosis. Because of their quick and high efficacy, the three anti-αIIbß3 drugs, abciximab, eptifibatide, and tirofiban, are regarded as potent anti-thrombotics and clinically approved by US Food and Drug Administration. However, because they interfere with the inside-out signaling of αIIbß3, which is required for stable platelet adhesion and aggregation, the application of abciximab, eptifibatide, and tirofiban is restricted to patients undergoing percutaneous coronary intervention. On the other hand, the outside-in signaling of αIIbß3 in platelets appears to be responsible for thrombus stabilization, and selective interference with the propagation of outside-in signals might signify a new therapeutic strategy to preferentially inhibit platelet-rich arterial thrombosis with less bleeding issues caused by way of compromised major hemostasis. The purpose of this review is to describe the bidirectional signal transduction of integrin αIIbß3 in platelets with a focus on outside-in signaling, more efficient and safer anti-αIIbß3 peptides, and the potential drug targets for future anti-platelet research.