title: A peptide isolated from alpha B-crystallin is a novel and potent inhibitor of platelet aggregation via dual prevention of PAR-1 and GPIb/V/IX.
abstract: BACKGROUND
  The ability of low-molecular-weight heat shock protein (HSP) to modulate thrombin-induced platelet aggregation has been investigated.
  
  
  OBJECTIVE
  We examined the inhibitory effects on platelet aggregation of nine amino acid sequences isolated from HSP20 or alpha B-crystallin and their various derivatives.
  
  
  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 alpha B-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.
  
  
  CONCLUSIONS
  Our results provide the basis for a potential new aspect of antiplatelet compound for the therapy of thrombosis and cardiovascular disease.
authors.affiliation: Department of Pharmacology, Gifu University School of Medicine, Japan. leuven@cc.gifu-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Matsuno
authors.forename: A
authors.initials: A
authors.lastname: Ishisaki
authors.forename: K
authors.initials: K
authors.lastname: Nakajima
authors.forename: K
authors.initials: K
authors.lastname: Kato
authors.forename: O
authors.initials: O
authors.lastname: Kozawa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006224:Cricetinae; D050886:HSP20 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000494:pharmacology; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D010750:Phosphoproteins / Q000494:pharmacology; D010973:Platelet Adhesiveness / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000037:antagonists & inhibitors*; D013917:Thrombin / Q000494:pharmacology; D013927:Thrombosis / Q000188:drug therapy / Q000517:prevention & control; D038203:alpha-Crystallin B Chain / Q000494:pharmacology*
chemical_list: D050886:HSP20 Heat-Shock Proteins; C494382:HSPB6 protein, human; D006360:Heat-Shock Proteins; D010446:Peptide Fragments; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D019038:Platelet Glycoprotein GPIb-IX Complex; D038203:alpha-Crystallin B Chain; D013917:Thrombin