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A peptide isolated from αB‐crystallin is a novel and potent inhibitor of platelet aggregation via dual prevention of PAR‐1 and GPIb/V/IX
Author(s) -
Matsuno H.,
Ishisaki A.,
Nakajima K.,
Kato K.,
Kozawa O.
Publication year - 2003
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2003.00502.x
Subject(s) - thrombin , chemistry , ristocetin , platelet , peptide , agonist , antithrombotic , receptor , dipeptide , pharmacology , von willebrand factor , biochemistry , amino acid , platelet aggregation inhibitor , protease , platelet membrane glycoprotein , platelet activation , aspirin , medicine , enzyme
Summary. 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 αB‐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 αB‐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.