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December 23, 2003BloodOpen Access

GPIb-dependent platelet activation is dependent on Src kinases but not MAP kinase or cGMP-dependent kinase

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Population

In vitro platelet assays and an in vivo rabbit model of thrombus formation

Comparison

cGMP-elevating agents, MAP kinase inhibitor, and… vs Control (implied)

Design

Preclinical

Authors

SMStuart MarshallCarnegie Mellon UniversityYSYotis A. SenisÉtablissement Français du SangJAJocelyn M. AugerUniversity of Port Harcourt

Discussion

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Overview

Src inhibition and sildenafil reduce thrombosis in rabbits; hypothesis-generating for human antithrombotic strategies pending clinical data.

Structured PICO

P
Population
In vitro platelet assays and an in vivo rabbit model of thrombus formation
I
Intervention
cGMP-elevating agents (glyco-SNAP-1, sildenafil), MAP kinase inhibitor (PD184161), and Src kinase inhibitor (PD173952)
C
Comparator
Control (implied)
O
Outcome
Activation of integrin alphaIIbbeta3, aggregate formation on collagen under flow conditions, and in vivo blood flowsurrogate

Src kinases, but not MAP kinases, are critical for VWF-dependent platelet activation, while cGMP-elevating agents like sildenafil inhibit this process.

Cite This Study

Marshall et al. (2003) studied this question.

synapsesocial.com/papers/6a75dde67d7eb453cc706ff6https://doi.org/10.1182/blood-2003-09-3319
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Also Consider

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  1. 1GPIbα-selective activation of platelets induces platelet signaling events comparable to GPVI activation events2010 · 51 citations
  2. 2Src family kinase–mediated and Erk-mediated thromboxane A2 generation are essential for VWF/GPIb-induced fibrinogen receptor activation in human platelets2005 · 121 citations
  3. 3A Mitogen-activated Protein Kinase-dependent Signaling Pathway in the Activation of Platelet Integrin αIIbβ32001 · 122 citations
  4. 4On the roles of cGMP and glycoprotein Ib in platelet activation2004 · 7 citations
  5. 5The role of Akt in the signaling pathway of the glycoprotein Ib-IX–induced platelet activation2007 · 146 citations