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 alpha B-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 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. CONCLUSION: Our results provide the basis for a potential new aspect of antiplatelet compound for the therapy of thrombosis and cardiovascular disease.
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 alpha B-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 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. CONCLUSION: Our results provide the basis for a potential new aspect of antiplatelet compound for the therapy of thrombosis and cardiovascular disease.
Authors: Catherine M Dreiza; Padmini Komalavilas; Elizabeth J Furnish; Charles R Flynn; Michael R Sheller; Christopher C Smoke; Luciana B Lopes; Colleen M Brophy Journal: Cell Stress Chaperones Date: 2009-07-01 Impact factor: 3.667
Authors: Lydia K Muranova; Maxim M Perfilov; Marina V Serebryakova; Nikolai B Gusev Journal: Cell Stress Chaperones Date: 2016-04-09 Impact factor: 3.667