Platelet activation via PAR4 is involved in the initiation of thrombin generation and in clot elasticity development

Autor: Tomas L. Lindahl, Sofia Ramström, Maria Bjerke, Karin Vretenbrant
Přispěvatelé: Clinical sciences
Jazyk: angličtina
Rok vydání: 2007
Předmět:
Medicin och hälsovetenskap
medicine.medical_treatment
Receptors
Thrombin/drug effects
Medical and Health Sciences
Reference Values
Protease-activated receptor
Platelet
Medicine(all)
biology
Chemistry
Thrombin
Hematology
Flow Cytometry
Platelet Activation/drug effects
Thrombelastography
Clotting time
Blood Platelets/drug effects
fibrinolysis
Oligopeptides
medicine.drug
circulatory and respiratory physiology
Blood Platelets
medicine.medical_specialty
Whole Blood Coagulation Time
Oligopeptides/pharmacology
In Vitro Techniques
Thrombomodulin
Fibrin
Antibodies
Internal medicine
Fibrinolysis
medicine
Humans
Receptor
PAR-1
Platelet activation
Blood Coagulation
Receptor
PAR-1/metabolism
Peptide Fragments/pharmacology
Thrombin/metabolism
Dose-Response Relationship
Drug
Fibrinogen
Platelet Activation
Peptide Fragments
Elasticity
Fibrinogen/metabolism
Endocrinology
Blood Coagulation/drug effects
Antibodies/pharmacology
biology.protein
Receptors
Thrombin
Popis: SummaryThrombin is a pivotal enzyme formed in the coagulation cascade and an important and potent platelet activator. The two pro-tease-activated thrombin receptors on human platelets are denoted PARI and PAR4. The physiological relevance of PAR4 is still unclear, as both aggregation and secretion can be accomplished by PARI activation alone. In the present study we have investigated the role of PARs in platelet activation, blood coagulation, clot elasticity and fibrinolysis. Flow cytometry, free oscillation rheometry and thrombin generation measurements were used to analyze blood or platelet-rich plasma from healthy individuals. Maximum PARI activation with the peptide SFLLRN gave fewer fibrinogen-binding platelets with lower mean fluorescent intensity than maximum PAR4 activation with AYPGKF. Inhibition of any of the receptors prolonged clotting times. However, PARI is more important for fibrinolysis; inhibition of this receptor prolonged all the steps in the fibrinolytic process. Clot elasticity decreased significantly when the PAR4 receptor was inhibited. In the thrombin generation measurements, PAR4 inhibition delayed the thrombin generation start and peak, but did not affect the total amount of thrombin generated. PAR I inhibition had no significant impact on thrombin generation. We found that PAR4 is most likely activated by low concentrations of thrombin during the initial phase of thrombin generation and is of importance to the clotting time. Furthermore, we suggest that the PAR4 receptor may have a physiological role in the stabilisation of the coagulum.
Databáze: OpenAIRE
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