Ubiquinol Effects on Antiphospholipid Syndrome Prothrombotic Profile A Randomized, Placebo-Controlled Trial

Objective-Antiphospholipid syndrome (APS) leukocytes exhibit an oxidative perturbation, directly linked to alterations in mitochondrial dynamics and metabolism. This disturbance is related to the patients' prothrombotic status and can be prevented by in vitro treatment with coenzyme Q10. Our aim was to investigate short-term effects of in vivo ubiquinol (reduced coenzyme Q(10) [Q(red)]) supplementation on markers related to inflammation and thrombosis in APS through a prospective, randomized, crossover, placebo-controlled trial. Approach and Results-Thirty-six patients with APS were randomized to receive Q(red) (200 mg/d) or placebo for 1 month. Thirty-three patients with APS completed the intervention, which increased plasma coenzyme Q(10). Q(red) improved endothelial function and decreased monocyte expression of prothrombotic and proinflammatory mediators, inhibited phosphorylation of thrombosis-related protein kinases, and decreased peroxides and percentage of monocytes with depolarized mitochondria; mitochondrial size was increased, and mitochondrial biogenesis-related genes were upregulated. Q(red) ameliorated extruded neutrophil extracellular traps in neutrophils and downregulated peroxides, intracellular elastase, and myeloperoxidase. Nanostring microRNA profiling revealed 20 microRNAs reduced in APS monocytes, and 16 of them, with a preponderance of cardiovascular disease-related target mRNAs, were upregulated. Monocytes gene profiling showed differential expression of 29 atherosclerosis-related genes, 23 of them changed by Q(red). Interaction networks of genes and microRNAs were identified. Correlation studies demonstrated co-ordinated effects of Q(red) on thrombosis and endothelial function-associated molecules. Conclusions-Our results highlight the potential of Q(red) to modulate the overexpression of inflammatory and thrombotic risk markers in APS. Because of the absence of clinically significant side effects and its potential therapeutic benefits, Q(red) might act as safe adjunct to standard therapies in APS. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT02218476 Visual Overview-An online visual overview is available for this article.