A peptide isolated from alpha B-crystallin is a novel and potent inhibitor of platelet aggregation via dual prevention of PAR-1 and GPlb/V/IX

Background: The ability of low-molecular-weight heat shock protein (HSP) to modulate thrombin-induced platelet aggregation has been investigated. Objectives: We examined the inhibitory effects on platelet aggregation of nine amino acid sequences isolated from HSP20 or alphabeta-crystallin and their various derivatives. Methods and results: Platelet aggregation induced by various agonists was performed. These findings indicated that a peptide (Trp-Ile-Arg-Arg-Pro-Phe-Phe-Pro-Phe) from alphabeta-crystallin significantly inhibits platelet aggregation induced by thrombin, TRAP (a protease activated receptor-1 agonist) and botrocetin, ristocetin (a stimulator of the platelet glycoprotein Ib/V/IX-von Willebrand factor axis), but not a protease-activated receptor-4 agonist, collagen and ADP. The inhibitory activity against thrombin or botrocetin is mainly linked to Arg-Arg-Pro-Phe or Trp-Ile-Arg-Arg-Pro, respectively, among nine amino acids. Additionally, during in vivo experiments, Trp-Ile-Arg-Arg-Pro-Phe-Phe-Pro-Phe shows a significant antithrombotic effect without marked bleeding. Conclusion: Our results provide the basis for a potential new aspect of antiplatelet compound for the therapy of thrombosis and cardiovascular disease.