What question did this study set out to answer?

To determine the dynamics and interdependence of PAR-1 and PAR-4 activation on human platelets stimulated with subnanomolar alpha-thrombin or receptor-activating peptides.

August 6, 2008Journal of Biological ChemistryOpen Access

Coordinate Activation of Human Platelet Protease-activated Receptor-1 and -4 in Response to Subnanomolar α-Thrombin

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Population

Human platelets

Design

Preclinical

Authors

FOFrederick A. OfosuGhana Health Service LDLori DewarMcMaster University SCSharon CravenCanadian Blood Services

Discussion

Member takes

Overview

Dual PAR-1/PAR-4 blockade may be required to inhibit low-dose thrombin platelet aggregation in animals; leaves open human antithrombotic translation.

Key Points

To determine the dynamics and interdependence of PAR-1 and PAR-4 activation on human platelets stimulated with subnanomolar alpha-thrombin or receptor-activating peptides.
Human platelets were stimulated with subnanomolar alpha-thrombin (≤1.0 nM) or selective receptor-activating peptides (10 µM SFLLRN, 100 µM AYPGKF).
PAR-1 and PAR-4 activation peptide release was quantified at 10 seconds post-stimulation.
Activation peptide release and platelet aggregation were evaluated in the presence of anti-PAR antibodies, the PAR-1 antagonist BMS 200261, or the PAR-4 antagonist YD3.
PAR-1 and PAR-4 activation peptides were detected within 10 seconds following exposure to ≤1.0 nM alpha-thrombin, SFLLRN, or AYPGKF.
Release of both activation peptides induced by 1.0 nM alpha-thrombin was significantly inhibited by anti-PAR-1-(35-62) IgY, anti-PAR-4-(34-54) IgY, and BMS 200261, but not by YD3.
Effective inhibition of platelet aggregation triggered by 1.0 nM alpha-thrombin occurred only when both anti-PAR antibodies were present simultaneously.

Structured PICO

Population

Human platelets

Intervention

Activation with ≤1.0 nM α-thrombin, 10 μM SFLLRN, or 100 μM AYPGKF, with or without PAR-1/PAR-4 inhibitors (anti-PAR-1-(35-62) IgY, anti-PAR-4-(34-54) IgY, BMS 200261, YD3)

Outcome

Generation of PAR-1 and -4 activation peptides and platelet aggregationsurrogate

Platelet activation by low-dose α-thrombin proceeds via simultaneous PAR-1 and PAR-4 activation, requiring dual inhibition to prevent platelet aggregation.

Cite This Study

Ofosu et al. (2008) studied this question.

synapsesocial.com/papers/6a764e2f3025cdd732bcbda7 https://doi.org/10.1074/jbc.m802237200

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August 6, 2008Journal of Biological ChemistryOpen Access

Coordinate Activation of Human Platelet Protease-activated Receptor-1 and -4 in Response to Subnanomolar α-Thrombin

View Full Paper

Ask AI

Bookmark

Population

Human platelets

Design

Preclinical

Authors

FOFrederick A. OfosuGhana Health Service LDLori DewarMcMaster University SCSharon CravenCanadian Blood Services

Discussion

Member takes

Overview

Dual PAR-1/PAR-4 blockade may be required to inhibit low-dose thrombin platelet aggregation in animals; leaves open human antithrombotic translation.

Key Points

To determine the dynamics and interdependence of PAR-1 and PAR-4 activation on human platelets stimulated with subnanomolar alpha-thrombin or receptor-activating peptides.
Human platelets were stimulated with subnanomolar alpha-thrombin (≤1.0 nM) or selective receptor-activating peptides (10 µM SFLLRN, 100 µM AYPGKF).
PAR-1 and PAR-4 activation peptide release was quantified at 10 seconds post-stimulation.
Activation peptide release and platelet aggregation were evaluated in the presence of anti-PAR antibodies, the PAR-1 antagonist BMS 200261, or the PAR-4 antagonist YD3.
PAR-1 and PAR-4 activation peptides were detected within 10 seconds following exposure to ≤1.0 nM alpha-thrombin, SFLLRN, or AYPGKF.
Release of both activation peptides induced by 1.0 nM alpha-thrombin was significantly inhibited by anti-PAR-1-(35-62) IgY, anti-PAR-4-(34-54) IgY, and BMS 200261, but not by YD3.
Effective inhibition of platelet aggregation triggered by 1.0 nM alpha-thrombin occurred only when both anti-PAR antibodies were present simultaneously.

Structured PICO

Population

Human platelets

Intervention

Activation with ≤1.0 nM α-thrombin, 10 μM SFLLRN, or 100 μM AYPGKF, with or without PAR-1/PAR-4 inhibitors (anti-PAR-1-(35-62) IgY, anti-PAR-4-(34-54) IgY, BMS 200261, YD3)

Outcome

Generation of PAR-1 and -4 activation peptides and platelet aggregationsurrogate

Platelet activation by low-dose α-thrombin proceeds via simultaneous PAR-1 and PAR-4 activation, requiring dual inhibition to prevent platelet aggregation.

Cite This Study

Ofosu et al. (2008) studied this question.

synapsesocial.com/papers/6a764e2f3025cdd732bcbda7 https://doi.org/10.1074/jbc.m802237200

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