coenzyme-q10 and Thrombosis

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.

Topics: Acetylcysteine; Anticoagulants; Antioxidants; Antiphospholipid Syndrome; Atherosclerosis; Autoantibodies; beta 2-Glycoprotein I; Coagulants; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Lupus Erythematosus, Systemic; Mitochondrial Diseases; Oxidative Stress; Reactive Oxygen Species; Recurrence; Thrombosis; Ubiquinone

Platelet integrin αIIbβ3 is the key mediator of atherothrombosis. Supplementation of coenzyme Q10 (CoQ10), a fat-soluble molecule that exists in various foods, exerts protective cardiovascular effects. This study aims to investigate whether and how CoQ10 acts on αIIbβ3 signaling and thrombosis, the major cause of cardiovascular diseases.. Through upregulating the platelet cAMP/PKA pathway, and attenuating αIIbβ3 signaling and thrombus growth, CoQ10 supplementation may play an important protective role in patients with risks of cardiovascular diseases.

Topics: Adult; Animals; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Cyclic Nucleotide Phosphodiesterases, Type 3; Double-Blind Method; Humans; Male; Mice; Mice, Inbred C57BL; Platelet Aggregation; Platelet Glycoprotein GPIIb-IIIa Complex; Receptor, Adenosine A2A; Signal Transduction; Thrombosis; Ubiquinone; Up-Regulation

A few case-stories claim that the anti-oxidant Coenzyme Q10 and possibly also Ginkgo biloba interact with warfarin treatment. A decreased response to warfarin in the Coenzyme Q10 cases and an increased response in the Ginkgo biloba case have been described.. Twenty-four outpatients on stable, long-term warfarin treatment were included in a randomised, double blind, placebo-controlled crossover trial. Coenzyme Q10 100 mg daily, Ginkgo-Biloba 100 mg daily and placebo were given in random order over treatment periods of four weeks, each followed by a two week wash out period. The international normalized ratio (INR) INR was kept between 2.0 and 4.0 by appropriate adjustment of the warfarin dosage.. Fourteen women and ten men, median ages 64.5 years (33-79) were included. Three patients withdrew from the study for personal reasons. The INR was stable during all treatment periods. The geometric mean dosage of warfarin did not change during the treatment periods: Ginkgo biloba 36.7 mg/week (95% confidence interval: 29.2-46.0); CoQ10 36.5 mg/week (29.1-45.8); placebo 36.0 mg/week (28.6-45.1).. The study indicated that Coenzyme Q10 and Ginkgo biloba do not influence the clinical effect of warfarin.

Topics: Adult; Aged; Anticoagulants; Antioxidants; Coenzymes; Cross-Over Studies; Double-Blind Method; Female; Ginkgo biloba; Humans; International Normalized Ratio; Male; Middle Aged; Phytotherapy; Plant Preparations; Thrombosis; Ubiquinone; Warfarin

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).

Topics: Adult; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Biomarkers; Case-Control Studies; Female; Humans; Immunoglobulin G; Inflammation; Male; Middle Aged; Mitochondria; Monocytes; Oxidative Stress; Peroxides; Thrombosis; Ubiquinone

Improved cardiovascular morbidity and mortality have been observed in several clinical studies of dietary supplementation with coenzyme Q10 (CoQ10, ubiquinone). Several mechanisms have been proposed to explain the effects of CoQ10. One attractive theory links ubiquinone with the inhibition of platelets. The effect of CoQ10 intake on platelet surface antigens, and certain hemostatic parameters was examined in 15 humans and 10 swine. Study participants received 100 mg of CoQ10 twice daily in addition to their usual diet for 20 days resulting in a three-fold increase of total serum CoQ10 level. We observed a decline in plasma fibronectin (-20.2%), thromboxane B2 (-20.6%), prostacyclin (-23.2%), and endothelin-1 (-17.9%) level. Significant inhibition of vitronectin receptor expression was observed consistently throughout ubiquinone treatment. Inhibition of the platelet vitronectin receptor is a direct evidence of a link between dietary CoQ10 intake, platelets, and hemostasis. These findings may contribute to the observed clinical benefits by a diminished incidence of thrombotic complications in such patients.

Topics: Animals; Coenzymes; Down-Regulation; Endothelin-1; Epoprostenol; Female; Fibronectins; Hemostasis; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Membrane Glycoproteins; Receptors, Vitronectin; Swine; Thrombosis; Thromboxane B2; Ubiquinone