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January 1, 2022International Journal of Molecular SciencesOpen Access

Role of Tyrosine Kinase Syk in Thrombus Stabilisation at High Shear

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Key result

Perfusion of the Syk inhibitor PRT-060318 over preformed thrombi enhanced thrombus breakdown and reduced thrombus contractile score as early as 3 minutes.

Why the study?

Understanding the pathways involved in the formation and stability of the core and shell regions of a platelet-rich arterial thrombus may lead to new ways to treat arterial thrombosis.

Does Syk inhibition reduce thrombus stability in human platelets under high shear flow?

Population

Preformed human platelet thrombi on collagen or atherosclerotic plaque homogenate at arterial shear

Comparison

Post-perfusion of Syk inhibitor PRT-060318 vs ticagrelor, indomethacin, dasatinib, ibrutinib, or GPVI nanobody Nb21

Design

In vitro flow-based assay

Authors

GPGina PerrellaSMSamantha J. MontagueHBHelena Brown

Discussion

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Member takes

Overview

May destabilize preformed arterial thrombi; hypothesis-generating for Syk inhibition in human high-shear thrombosis.

Structured PICO

Does Syk inhibition reduce thrombus stability in human platelets under high shear flow?

P
Population
Human platelets forming thrombi on collagen or atherosclerotic plaque homogenate at arterial shear (1000 s−1) in vitro
I
Intervention
Syk inhibitor PRT-060318 post-perfusion over preformed thrombi
C
Comparator
Other inhibitors (ticagrelor, indomethacin, dasatinib, ibrutinib, GPVI nanobody Nb21) or control
O
Outcome
Thrombus stability (measured by thrombus breakdown, platelet detachment, and thrombus contractile score)surrogate

Syk regulates arterial thrombus stability in the absence of fibrin, suggesting Syk inhibition as a potential novel pathway to treat arterial thrombosis.

Cite This Study

Perrella et al. (2022) studied Arterial thrombosis. Syk inhibitor PRT-060318 was evaluated on Thrombus stability and contractile score. Perfusion of the Syk inhibitor PRT-060318 over preformed thrombi enhanced thrombus breakdown and reduced thrombus contractile score as early as 3 minutes.

synapsesocial.com/papers/6a8441a474ee596ff2c5226ehttps://doi.org/10.3390/ijms23010493
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Platelets undergo phosphorylation of Syk at Y525/526 and Y352 in response to pathophysiological shear stress2008 · 31 citations
  2. 2Role of Platelet Glycoprotein VI and Tyrosine Kinase Syk in Thrombus Formation on Collagen-Like Surfaces2019 · 47 citations
  3. 3Inhibition of Src but not Syk causes weak reversal of GPVI-mediated platelet aggregation measured by light transmission aggregometry2022 · 4 citations
  4. 4Stabilizing Role of Platelet P2Y12 Receptors in Shear-Dependent Thrombus Formation on Ruptured Plaques2010 · 50 citations
  5. 5Platelet PI3Kβ and GSK3 regulate thrombus stability at a high shear rate2014 · 88 citations