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August 21, 2008AJP Cell Physiology

Platelets undergo phosphorylation of Syk at Y525/526 and Y352 in response to pathophysiological shear stress

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Key result

Pharmacological inhibition of Syk attenuated shear-induced platelet aggregation and reduced platelet-mediated thrombus formation by up to 50% under flow conditions.

Why the study?

Does Syk inhibition reduce shear-induced platelet aggregation and thrombus formation under pathophysiological shear stress?

Population

Isolated human platelets and whole blood

Comparison

Pathophysiological shear stress and… vs Physiological shear stress and untreated controls

Design

Preclinical

Authors

HSHenry E. SpeichSGSvetozar GrgurevichTKTeddi J. Kueter

Discussion

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Overview

Syk inhibition may attenuate shear-induced thrombosis in animal models; leaves open translation to clinical occlusive vascular disease.

Structured PICO

Does Syk inhibition reduce shear-induced platelet aggregation and thrombus formation under pathophysiological shear stress?

P
Population
Isolated human platelets and whole blood
I
Intervention
Pathophysiological shear stress (100 dyn/cm2) and pharmacological inhibition of Syk using piceatannol and OXSI-2
C
Comparator
Physiological shear stress (10 dyn/cm2) and untreated controls
O
Outcome
Syk tyrosine phosphorylation at Y525/526 and Y352, shear-induced platelet aggregation (SIPA), and platelet-mediated thrombus formationsurrogate

Syk is a key molecule in shear-induced platelet aggregation and thrombus formation, suggesting its pharmacological inhibition may be a potential therapeutic target for occlusive vascular disease.

Cite This Study

Speich et al. (2008) studied Shear-induced platelet aggregation. Syk inhibitors (piceatannol and OXSI-2) vs. Untreated/control was evaluated on Syk tyrosine phosphorylation and platelet-mediated thrombus formation. Pharmacological inhibition of Syk attenuated shear-induced platelet aggregation and reduced platelet-mediated thrombus formation by up to 50% under flow conditions.

synapsesocial.com/papers/6a20fa59b86afc18201823efhttps://doi.org/10.1152/ajpcell.90644.2007
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Also Consider

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

  1. 1Primary arrest of circulating platelets on collagen involves phosphorylation of Syk, cortactin and focal adhesion kinase: studies under flow conditions2002 · 13 citations
  2. 2Blockade of adenosine diphosphate receptors P2Y12 and P2Y1 is required to inhibit platelet aggregation in whole blood under flow2001 · 145 citations
  3. 3Increased Shear Stress Overcomes the Antithrombotic Platelet Inhibitory Effect of Aspirin in Stenosed Dog Coronary Arteries1996 · 90 citations
  4. 4Optimal Antagonism of GPIIb/IIIa Favors Platelet Adhesion by Inhibiting Thrombus Growth1996 · 30 citations
  5. 5FcRγ Presence in TCR Complex of Double-Negative T Cells Is Critical for Their Regulatory Function2006 · 24 citations