Title:Anti-Platelet Peptides Targeting αIIbβ3 Outside-In Signaling Pathway
Volume: 24
Issue: 1
Author(s): Jialing Wang and Xin Xu*
Affiliation:
- Laboratory for Stem Cell and Regenerative Medicine, School of Life Science and Technology, Weifang Medical University,
Weifang, China
Keywords:
Platelet, peptides, αIIbβ3, bidirectional signal, outside-in signaling, arterial thrombosis, bleeding.
Abstract: Platelets and their progenitors express high levels of integrin αIIbβ3, which plays a key role
in platelet functions, hemostasis, and arterial thrombosis. Because of their quick and high efficacy, the
three anti-αIIbβ3 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 αIIbβ3, 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 αIIbβ3 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 αIIbβ3 in platelets with a focus on
outside-in signaling, more efficient and safer anti-αIIbβ3 peptides, and the potential drug targets for
future anti-platelet research.
