title: Mitochondrial dysfunction in antiphospholipid syndrome: implications in the pathogenesis of the disease and effects of coenzyme Q(10) treatment.
abstract: The exact mechanisms underlying the role of oxidative stress in the pathogenesis and the prothrombotic or proinflammatory status of antiphospholipid syndrome (APS) remain unknown. Here, we investigate the role of oxidative stress and mitochondrial dysfunction in the proatherothrombotic status of APS patients induced by IgG-antiphospholipid antibodies and the beneficial effects of supplementing cells with coenzyme Q(10) (CoQ(10)). A significant increase in relevant prothrombotic and inflammatory parameters in 43 APS patients was found compared with 38 healthy donors. Increased peroxide production, nuclear abundance of Nrf2, antioxidant enzymatic activity, decreased intracellular glutathione, and altered mitochondrial membrane potential were found in monocytes and neutrophils from APS patients. Accelerated atherosclerosis in APS patients was found associated with their inflammatory or oxidative status. CoQ(10) preincubation of healthy monocytes before IgG-antiphospholipid antibody treatment decreased oxidative stress, the percentage of cells with altered mitochondrial membrane potential, and the induced expression of tissue factor, VEGF, and Flt1. In addition, CoQ(10) significantly improved the ultrastructural preservation of mitochondria and prevented IgG-APS-induced fission mediated by Drp-1 and Fis-1 proteins. In conclusion, the oxidative perturbation in APS patient leukocytes, which is directly related to an inflammatory and pro-atherothrombotic status, relies on alterations in mitochondrial dynamics and metabolism that may be prevented, reverted, or both by treatment with CoQ(10).
authors.affiliation: Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC)-Reina Sofia Hospital, Cordoba, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Perez-Sanchez
authors.forename: Patricia
authors.initials: P
authors.lastname: Ruiz-Limon
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Aguirre
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Bertolaccini
authors.forename: Munther A
authors.initials: MA
authors.lastname: Khamashta
authors.forename: Antonio
authors.initials: A
authors.lastname: Rodriguez-Ariza
authors.forename: Pedro
authors.initials: P
authors.lastname: Segui
authors.forename: Eduardo
authors.initials: E
authors.lastname: Collantes-Estevez
authors.forename: Nuria
authors.initials: N
authors.lastname: Barbarroja
authors.forename: Husam
authors.initials: H
authors.lastname: Khraiwesh
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Gonzalez-Reyes
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Villalba
authors.forename: Francisco
authors.initials: F
authors.lastname: Velasco
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Cuadrado
authors.forename: Chary
authors.initials: C
authors.lastname: Lopez-Pedrera
mesh_terms: D000328:Adult; D017152:Antibodies, Antiphospholipid / Q000494:pharmacology; D016736:Antiphospholipid Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007249:Inflammation / Q000150:complications / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010545:Peroxides / Q000378:metabolism; D013927:Thrombosis / Q000150:complications / Q000473:pathology; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D017152:Antibodies, Antiphospholipid; D015415:Biomarkers; D007074:Immunoglobulin G; D010545:Peroxides; D014451:Ubiquinone; C024989:coenzyme Q10