Antiphospholipid syndrome and tissue factor: a thrombotic couple.
The antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy morbidity in the presence of antiphospholipid antibodies (aPL). Among the thrombogenic mechanisms proposed, it has been suggested that aPL can stimulate tissue factor (TF) expression by endothelial cells (ECs) and monocytes. Moreover, our in vivo studies have shown that APS patients (particularly those with thrombosis) have increased monocyte TF expression. Yet, the molecular mechanism(s) by which aPL induce TF expression has not been completely underscored. In a recent study, we have demonstrated that aPL induces TF expression in monocytes from APS patients by activating, simultaneously and independently, the phosphorylation of MEK-1/ERK proteins, and the p38 MAP kinase-depenent nuclear translocation and activation of NFkappaB/Rel proteins. Understanding the intracellular mechanism(s) of aPL-mediated monocyte activation may help to establish new therapeutic approaches, such as selective inhibition of MAP kinases, to reverse the prothrombotic state in APS. Furthermore, the contribution of TF to a protrombotic state in the APS provides a renewed focus on antithrombotic therapies in current use, including the oral anticoagulation and, more recently, the use of statins, which have been proven to be effective in the inhibition of EC and monocyte TF-expression.
López-Pedrera
Ch
Ch
Research Unit and Rheumatology Department, Reina Sofia Hospital, Córdoba, Spain. rosario.lopez.exts@juntadeandalucia.es
Buendía
P
P
Aguirre
M A
MA
Velasco
F
F
Cuadrado
M J
MJ
D017152:Antibodies, Antiphospholipid / Q000502:physiology; D016736:Antiphospholipid Syndrome / Q000150:complications* / Q000188:drug therapy; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D013925:Thromboplastin / Q000037:antagonists & inhibitors / Q000502:physiology*; D013927:Thrombosis / Q000209:etiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
D017152:Antibodies, Antiphospholipid; D013925:Thromboplastin; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases