Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Mitochondrial Dysfunction in Monocytes From Antiphospholipid Syndrome Patients: Implications in the Pathogenesis of the Disease and Effects of Coenzyme Q Treatment.
Lopez-Pedrera1, Chary, Perez-Sanchez1, Carlos, Ruiz-Limon1, Patricia, Aguirre1, Ma Angeles, Carretero1, Rosario Ma, Barbarroja1, Nuria, Rodriguez-Ariza1, Antonio
IMIBIC-Reina Sofia Hospital, Cordoba, Spain
University of Cordoba, Cordoba, Spain
Lupus Research Unit, The Rayne Institute, Kings College London School of Medicine, London, United Kingdom
The Rayne Institute, London, United Kingdom
Recent studies have evidenced that oxidative stress may play a role in the pathophysiology of APS. However it is still not clear whether oxidative stress is the cause or the effect of the prothrombotic/proinflamatory status of APS. Furthermore, the precise role of mitochondria in the redox imbalance reported in APS remains unknown. Aim: We undertook this study to investigate the role of mitochondrial dysfunction and oxidative stress in aPL-induced prothrombotic status in APS patients, and to test the effects of supplementing cells with coenzyme Q10 (CoQ10), a well established mitochondrial cofactor and antioxidant.
We studied 25 patients and 25 healthy controls. Mitochondrial function in monocytes was analyzed by measuring mitochondrial membrane potential (MMP) with flow cytometry. Oxidative stress was determined by quantifying peroxide and peroxynitrite generation, intracellular glutathione, nitric oxide (NO), and N-Tyr in monocytes and plasma. Various parameters related to thrombosis and inflammation, as well as the intracellular pathways involved were also tested. Mitochondrial function was evaluated through in vitro studies in which purified monocytes were preincubated with CoQ10, followed by stimulation with purified IgG from 7 APS patients (aPL-IgG). We also studied mitochondrial dynamics in monocytes treated with aPL-IgG in the presence or in the absence of CoQ10, by measuring cellular levels of proteins controlling mitochondrial fission (Drp-1, Fis1, and Opa-1) or fusion (Mfn-1 and Mfn-2). Mitochondrial alterations were also studied by electron microscopy.
CoQ10 decreased significantly the percentage of cells with altered MMP as well as the production of ROS and aPL-IgG-induced production of peroxides. CoQ10 treatment also affected significantly the aPL-IgG induced expression of TF, VEGF and Flt1, as well as the intracellular signalling pathways regulating their expression. Treatment of monocytes with aPL-IgG consistently upregulated proteins involved in mitochondrial fission, and these alterations were reversed by pre-treatment with CoQ10. Monocytes treated with aPL-IgG contained rounded mitochondria, and figures evidencing mitochondrial fission were readily observed. Monocytes pretreated with CoQ10 contained elongated mitochondria with significantly improved ultrastructure.
The binding of aPL-IgG to monocytes membrane elicites a redox-signalling pathway in which mitochondrial activity is compromised, and dynamics is altered towards enhanced rates of mitochondrial fission. The induced mitochondrial dysfunction, which is prevented by CoQ10, seems to be directly involved in the aPL-induced monocyte activation. Supported by JA0246/2009, P08CVI04234 and PS09/01809.
To cite this abstract, please use the following information:
Lopez-Pedrera, Chary, Perez-Sanchez, Carlos, Ruiz-Limon, Patricia, Aguirre, Ma Angeles, Carretero, Rosario Ma, Barbarroja, Nuria, et al; Mitochondrial Dysfunction in Monocytes From Antiphospholipid Syndrome Patients: Implications in the Pathogenesis of the Disease and Effects of Coenzyme Q Treatment. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :725