title: The role of TLR4 in pathophysiology of antiphospholipid syndrome-associated thrombosis and pregnancy morbidity.
abstract: The antiphospholipid syndrome (APS) is an autoimmune disease characterized by the clinical features of recurrent thrombosis in the venous or arterial circulation and fetal losses. Antiphospholipid antibodies (aPL), particularly against the phospholipid binding protein beta-2 glycoprotein I (β2GPI), play an important role in APS pathological mechanisms. aPL can activate intracellular signal transduction in a β2GPI-dependent manner to induce inflammatory responses, and promote hypercoagulable state and recurrent spontaneous abortion when β2GPI is associated with the cell surface receptor. In vivo and in vitro studies show that Annexin A2 (ANXA2) is the high affinity receptor that connects β2GPI to the target cells. However, ANXA2 is not a transmembrane protein and lacks an intracellular signal transduction pathway. Growing evidences suggest that the transmembrane protein toll-like receptor 4 (TLR4) might act as an 'adaptor' for intracellular signal transduction. This review focuses on the role of TLR4 and its signalling pathway in APS pathological mechanisms which will help us better understand the pathological processes of this syndrome.
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China; Department of Clinical Laboratory and Haematology, School of Medical Science and Laboratory Medicine of Jiangsu University, Zhenjiang, China.
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Xie
authors.forename: Liangju
authors.initials: L
authors.lastname: Sheng
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.forename: Jinchuan
authors.initials: J
authors.lastname: Yan
mesh_terms: D017306:Annexin A2 / Q000276:immunology / Q000378:metabolism; D017152:Antibodies, Antiphospholipid / Q000276:immunology / Q000378:metabolism; D016736:Antiphospholipid Syndrome / Q000150:complications* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology*; D015398:Signal Transduction; D013927:Thrombosis / Q000209:etiology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D053482:beta 2-Glycoprotein I / Q000276:immunology / Q000378:metabolism
chemical_list: D017306:Annexin A2; D017152:Antibodies, Antiphospholipid; D051197:Toll-Like Receptor 4; D053482:beta 2-Glycoprotein I
keywords: antiphospholipid syndrome; beta-2 glycoprotein I; coagulation factor III (tissue factor); nuclear factor-κB; toll-like receptor 4