Pravastatin and C reactive protein modulate protease- activated receptor-1 expression in vitro blood platelets

Cell Mol Biol (Noisy-le-grand). 2016 Feb 29;62(2):75-80.

Abstract

Protease-activated receptor-1 (PAR-1) plays an important role in mediating activation of human platelets by thrombin. However, mechanism of statin in ADP-induced platelet PAR-1 expression is also unknown. Aggregometry, flow cytometry, immunoblotting and ELISA were used to determine role of pravastatin participating in ADP-induced platelet activation and PAR-1 expression. ADP stimulation significantly increased PAR-1 expression on platelets. PAR-1 antagonist SCH-79797 inhibited platelet aggregation as well as decreased platelet P-selectin expression induced by ADP. CRP inhibited PAR-1 expression induced by ADP in a concentration-dependent manner. Pravastatin treatment reduced PAR-1 expression in a concentration-dependent manner. Combination treatment of CRP and Pravastatin significantly reduced platelet PAR-1 expression induced by ADP. By western-blot analysis, pravastatin treatment did not influence total PAR-1 after ADP treatment. CRP decreased platelet total PAR-1 expression induced by ADP. Pravastatin and CRP reduced TXB2 formation by ADP significantly. CRP decreased thrombin fragment F1+2 level with ADP treatment. Pravastatin, in contrast, did not influence F1+2 level. Upon treatment with Pravastatin reduced platelet LOX-1 expression induced by ADP. In conclusion, PAR-1 served as a critical mechanism to relay platelet activation process induced by ADP. CRP and pravastatin reduce PAR-1 expression in platelet by ADP pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / pharmacology
  • Blood Platelets / cytology
  • Blood Platelets / metabolism*
  • C-Reactive Protein / pharmacology*
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Gene Expression Regulation / drug effects*
  • Humans
  • Immunoblotting
  • P-Selectin / genetics
  • P-Selectin / metabolism
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors
  • Pravastatin / pharmacology*
  • Pyrroles / pharmacology
  • Quinazolines / pharmacology
  • Receptor, PAR-1 / metabolism*
  • Receptors, Thromboxane A2, Prostaglandin H2 / genetics
  • Receptors, Thromboxane A2, Prostaglandin H2 / metabolism
  • Scavenger Receptors, Class E / genetics
  • Scavenger Receptors, Class E / metabolism
  • Thrombin / metabolism

Substances

  • N3-cyclopropyl-7-((4-(1-methylethyl)phenyl)methyl)-7H-pyrrolo(3, 2-f)quinazoline-1,3-diamine
  • OLR1 protein, human
  • P-Selectin
  • Pyrroles
  • Quinazolines
  • Receptor, PAR-1
  • Receptors, Thromboxane A2, Prostaglandin H2
  • Scavenger Receptors, Class E
  • Adenosine Diphosphate
  • C-Reactive Protein
  • Thrombin
  • Pravastatin
  • Platelet Aggregation Inhibitors