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Antiphospholipid syndrome and tissue factor: a thrombotic couple
Ch López-Pedrera1, P Buendía, M A Aguirre
1Research Unit and Rheumatology Department, Reina Sofia Hospital, Córdoba, Spain. rosario.lopez.exts@juntadeandalucia.es
Lupus
|April 26, 2006
Summary
Antiphospholipid syndrome (APS) involves blood clots and pregnancy issues due to antiphospholipid antibodies (aPL). These antibodies activate monocytes, increasing tissue factor (TF) expression and thrombosis risk via specific cellular pathways.
Area of Science:
- Immunology
- Vascular Biology
- Molecular Medicine
Background:
- Antiphospholipid syndrome (APS) is defined by thrombosis and/or pregnancy complications associated with antiphospholipid antibodies (aPL).
- Tissue factor (TF) expression by endothelial cells and monocytes is a proposed mechanism for aPL-induced thrombosis.
- Previous in vivo studies indicated elevated monocyte TF expression in APS patients, particularly those with thrombosis.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying aPL-induced TF expression in monocytes from APS patients.
- To identify intracellular signaling pathways involved in aPL-mediated monocyte activation.
Main Methods:
- Monocytes from APS patients were analyzed for TF expression.
- Intracellular signaling pathways, including MEK-1/ERK and p38 MAP kinase/NFkappaB/Rel, were investigated in response to aPL stimulation.
Main Results:
- Antiphospholipid antibodies (aPL) were shown to induce TF expression in monocytes from APS patients.
- This induction was mediated by the simultaneous and independent activation of MEK-1/ERK phosphorylation and p38 MAP kinase-dependent NFkappaB/Rel nuclear translocation and activation.
Conclusions:
- Understanding the intracellular mechanisms of aPL-induced monocyte activation is crucial for developing targeted therapies.
- Selective inhibition of MAP kinases presents a potential therapeutic strategy to mitigate the prothrombotic state in APS.
- TF's role in APS thrombosis highlights the importance of existing antithrombotic therapies like anticoagulation and statins, which inhibit TF expression.