title: Pravastatin and C reactive protein modulate protease- activated receptor-1 expression in vitro blood platelets.
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.
authors.affiliation: The Fourth Affiliated Hospital of Guangxi Medical University Department of Cardiology Liuzhou China chullxiang@sina.com.
authors.forename: L-X
authors.initials: LX
authors.lastname: Chu
authors.affiliation: Affiliated Hospital of Guilin Medical College Department of Endocrine Guilin China.
authors.forename: S-X
authors.initials: SX
authors.lastname: Zhou
authors.affiliation: The Fourth Affiliated Hospital of Guangxi Medical University Department of Cardiology Liuzhou China.
authors.forename: F
authors.initials: F
authors.lastname: Yang
authors.affiliation: The Fourth Affiliated Hospital of Guangxi Medical University Department of Cardiology Liuzhou China.
authors.forename: Y-Q
authors.initials: YQ
authors.lastname: Qin
authors.affiliation: The Fourth Affiliated Hospital of Guangxi Medical University Department of Cardiology Liuzhou China.
authors.forename: Z-S
authors.initials: ZS
authors.lastname: Liang
authors.affiliation: The Eighth Affiliated Hospital of Guangxi Medical University Department of Cardiology Guigang China.
authors.forename: C-G
authors.initials: CG
authors.lastname: Mo
authors.affiliation: The Fourth Affiliated Hospital of Guangxi Medical University Department of Cardiology Liuzhou China.
authors.forename: X-D
authors.initials: XD
authors.lastname: Wang
authors.affiliation: The Fourth Affiliated Hospital of Guangxi Medical University Department of Cardiology Liuzhou China.
authors.forename: J
authors.initials: J
authors.lastname: Xie
authors.affiliation: The Fourth Affiliated Hospital of Guangxi Medical University Department of Cardiology Liuzhou China.
authors.forename: L-P
authors.initials: LP
authors.lastname: He
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D002097:C-Reactive Protein / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D015151:Immunoblotting; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D017035:Pravastatin / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D044463:Receptor, PAR-1 / Q000378:metabolism*; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000235:genetics / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors
chemical_list: C415424:N3-cyclopropyl-7-((4-(1-methylethyl)phenyl)methyl)-7H-pyrrolo(3, 2-f)quinazoline-1,3-diamine; C495137:OLR1 protein, human; D019007:P-Selectin; D011758:Pyrroles; D011799:Quinazolines; D044463:Receptor, PAR-1; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D051127:Scavenger Receptors, Class E; D000244:Adenosine Diphosphate; D002097:C-Reactive Protein; D013917:Thrombin; D017035:Pravastatin; D010975:Platelet Aggregation Inhibitors