title: New Insights in the Pathophysiology of Antiphospholipid Syndrome.
abstract: The antiphospholipid syndrome (APS) is an autoimmune disorder characterized by an elevated risk for arterial and venous thrombosis and pregnancy-related morbidity. Since the discovery of the disease in 1980s, numerous studies in cell culture systems, in animal models, and in patient populations have been reported, leading to a deeper understanding of the pathogenesis of APS. These studies have determined that circulating autoantibodies, collectively called antiphospholipid antibodies (aPL), the majority of which recognize cell surface proteins attached to the plasma membrane phospholipids, play a causal role in the development of the disease. The binding of aPL to the cell surface antigens triggers interaction of the complex with transmembrane receptors to initiate intracellular signaling in critical cell types, including platelets, monocytes, endothelial cells, and trophoblasts. Subsequent alteration of various cell functions results in inflammation, thrombus formation, and pregnancy complications. Apolipoprotein E receptor 2 (apoER2), a lipoprotein receptor family member, has been implicated as a mediator for aPL actions in platelets and endothelial cells. Nitric oxide (NO) is a signaling molecule known to exert potent antithrombotic, anti-inflammatory, and anti-atherogenic effects. NO insufficiency and oxidative stress have been linked to APS pathogenesis. This review will focus on the recent findings on how apoER2 and dysregulation of NO production contribute to aPL-mediated pathologies in APS.
authors.affiliation: Department of Pediatrics, Center for Pulmonary and Vascular Biology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Sacharidou
authors.affiliation: Department of Pediatrics, Center for Pulmonary and Vascular Biology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Shaul
authors.affiliation: Department of Pediatrics, Center for Pulmonary and Vascular Biology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Chieko
authors.initials: C
authors.lastname: Mineo
mesh_terms: D016736:Antiphospholipid Syndrome / Q000503:physiopathology*; D005260:Female; D006801:Humans