Key result
Deletion or pharmacological inhibition of platelet PI3Kβ caused thrombus instability and embolization at high shear rates, which was restored by GSK3 inhibition.
Why the study?
Does PI3Kβ inhibition affect thrombus stability at high shear rates in preclinical models?
Population
Mice with selective p110β deletion in the megakaryocyte lineage and human blood samples
Comparison
Genetic deletion of p110β or pharmacologic… vs Wild-type mice or untreated human blood (implied)
Design
Preclinical
Authors
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May promote embolization with PI3Kβ inhibition at high shear; leaves open clinical relevance for antithrombotic development.
Does PI3Kβ inhibition affect thrombus stability at high shear rates in preclinical models?
PI3Kβ plays a critical role in maintaining thrombus integrity at high arterial shear rates, suggesting that PI3Kβ inhibitors may carry a risk of embolization.
Laurent et al. (2014) studied Arterial thrombosis. PI3Kβ deletion or inhibition (AZD6482) vs. Wild-type or untreated control was evaluated on Thrombus stability at high shear rate. Deletion or pharmacological inhibition of platelet PI3Kβ caused thrombus instability and embolization at high shear rates, which was restored by GSK3 inhibition.
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