title: Oxidative stress in the pathogenesis of atherothrombosis associated with anti-phospholipid syndrome and systemic lupus erythematosus: new therapeutic approaches.
abstract: Atherothrombosis is a recurrent complication in APS and SLE patients. Oxidative stress has been suggested as a key player underlying this process. Autoantibodies have been pointed to as the main contributors to abnormality in the oxidative status observed in APS and SLE patients, promoting the increased production of oxidant species and the reduction of antioxidant molecules. This imbalance causes vascular damage through the activation of immune cells, including monocytes, lymphocytes and neutrophils, causing the expression of pro-inflammatory and procoagulant molecules, the formation of neutrophil extracellular traps and the adhesion of these cells to the endothelium; the induction of cellular apoptosis and impaired cell clearance, which in turn enhances autoantibody neogeneration; and cytotoxicity of endothelial cells. This review describes the mechanisms underlying the role of oxidative stress in the pathogenesis of atherothrombosis associated with APS and SLE, focused on the effect of autoantibodies, the different cell types involved and the diverse effectors, including cytokines, procoagulant proteins and their main modulators, such as oxidant/antioxidant species and intracellular pathways in each pathology. We further discuss new therapies aimed at restoring the oxidative stress balance and subsequently to tackle atherothrombosis in APS and SLE.
authors.affiliation: Maimonides Institute for Research in Biomedicine of Cordoba, Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain rosario.lopez.exts@juntadeandalucia.es.
authors.forename: Chary
authors.initials: C
authors.lastname: López-Pedrera
authors.affiliation: Maimonides Institute for Research in Biomedicine of Cordoba, Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Barbarroja
authors.affiliation: Maimonides Institute for Research in Biomedicine of Cordoba, Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Jimenez-Gomez
authors.affiliation: Maimonides Institute for Research in Biomedicine of Cordoba, Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Collantes-Estevez
authors.affiliation: Maimonides Institute for Research in Biomedicine of Cordoba, Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain.
authors.forename: Ma Angeles
authors.initials: MA
authors.lastname: Aguirre
authors.affiliation: Rheumatology Service, St Thomas Hospital, Lupus Research Unit, London, UK.
authors.forename: Ma Jose
authors.initials: MJ
authors.lastname: Cuadrado
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use; D000925:Anticoagulants / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D016736:Antiphospholipid Syndrome / Q000150:complications*; D050197:Atherosclerosis / Q000188:drug therapy / Q000209:etiology*; D001323:Autoantibodies / Q000502:physiology; D003029:Coagulants / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007249:Inflammation / Q000503:physiopathology; D008180:Lupus Erythematosus, Systemic / Q000150:complications*; D028361:Mitochondrial Diseases / Q000209:etiology; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012008:Recurrence; D013927:Thrombosis / Q000188:drug therapy / Q000209:etiology*; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000627:therapeutic use; D053482:beta 2-Glycoprotein I / Q000378:metabolism / Q000502:physiology
chemical_list: D000925:Anticoagulants; D000975:Antioxidants; D001323:Autoantibodies; D003029:Coagulants; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017382:Reactive Oxygen Species; D053482:beta 2-Glycoprotein I; D014451:Ubiquinone; C024989:coenzyme Q10; D000111:Acetylcysteine
keywords: anti-phospholipid syndrome; atherothrombosis; oxidative stress; systemic lupus erythematosus; therapeutic approaches