López-Pedrera Ch, Buendía P, Aguirre M A, Velasco F, Cuadrado M J
Research Unit and Rheumatology Department, Reina Sofia Hospital, Córdoba, Spain.
Lupus. 2006;15(3):161-6. doi: 10.1191/0961203306lu2276rr.
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.
抗磷脂综合征（APS）的特征是在存在抗磷脂抗体（aPL）的情况下发生血栓形成和/或妊娠并发症。在提出的血栓形成机制中，有人认为aPL可刺激内皮细胞（EC）和单核细胞表达组织因子（TF）。此外，我们的体内研究表明，APS患者（尤其是有血栓形成的患者）单核细胞TF表达增加。然而，aPL诱导TF表达的分子机制尚未完全阐明。在最近的一项研究中，我们证明aPL通过同时且独立地激活MEK-1/ERK蛋白的磷酸化以及p38 MAP激酶依赖的NFkappaB/Rel蛋白的核转位和激活，诱导APS患者单核细胞中的TF表达。了解aPL介导的单核细胞激活的细胞内机制可能有助于建立新的治疗方法，例如选择性抑制MAP激酶，以逆转APS中的血栓前状态。此外，TF在APS血栓前状态中的作用使人们重新关注目前使用的抗血栓治疗方法，包括口服抗凝治疗，以及最近使用的他汀类药物，这些药物已被证明可有效抑制EC和单核细胞TF表达。
