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April 1, 2022BloodOpen Access

Both G protein–coupled and immunoreceptor tyrosine-based activation motif receptors mediate venous thrombosis in mice

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Key result

Inhibiting GPCR or ITAM platelet signaling pathways reduces venous thrombosis in mice.

Why the study?

Platelets contribute to venous thrombosis, but the underlying signaling mechanisms distinct from arterial thrombosis are largely unknown.

Does inhibition of GPCR and ITAM receptor signaling reduce venous thrombosis in mice?

Population

Wild-type and transgenic mice

Comparison

Inhibitors of platelet-signaling pathways vs control or single pathway inhibition

Design

Preclinical experimental study

Authors

JMJean-Marie MwizaRLRobert Hugh LeeDPDavid S. Paul

Discussion

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Member takes

Overview

Supports platelet signaling inhibition as a venous thrombosis target; leaves open translation to human disease.

Structured PICO

Does inhibition of GPCR and ITAM receptor signaling reduce venous thrombosis in mice?

P
Population
Wild-type and transgenic mice evaluated for venous thrombosis induced by inferior vena cava stenosis.
I
Intervention
Inhibitors of platelet-signaling pathways: ITAM-CLEC2 (Clec2mKO), glycoprotein VI (JAQ1 antibody), Bruton's tyrosine kinase (ibrutinib), GPCR-cyclooxygenase 1 (aspirin), and P2Y12 (clopidogrel)
C
Comparator
Control mice or single pathway inhibition
O
Outcome
Thrombus weights after inferior vena cava stenosissurrogate

Venous thrombosis initiation requires platelet activation via both GPCRs and ITAM receptors, and strong inhibition of either pathway reduces venous thrombosis in mice.

Cite This Study

Mwiza et al. (2022) studied Venous thrombosis. Inhibition of platelet GPCR and ITAM receptor signaling vs. Control or single pathway inhibition was evaluated on Thrombus weights. Strong inhibition of either GPCR or ITAM platelet signaling pathways reduced venous thrombosis in mice.

synapsesocial.com/papers/6ab48757fbdb072f4eeb74d9https://doi.org/10.1182/blood.2022015787
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