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

Carlos Pérez-Sánchez; María Ángeles Aguirre; Patricia Ruiz-Limón; María Carmen Ábalos-Aguilera; Yolanda Jiménez-Gómez; Iván Arias-de la Rosa; Antonio Rodriguez-Ariza; Lucía Fernández-Del Río; José Antonio González-Reyes; Pedro Segui; Eduardo Collantes-Estévez; Nuria Barbarroja; Francisco Velasco; Savino Sciascia; Irene Cecchi; María José Cuadrado; José Manuel Villalba; Chary López-Pedrera

doi:10.1161/ATVBAHA.117.309225

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

Arterioscler Thromb Vasc Biol. 2017 Oct;37(10):1923-1932. doi: 10.1161/ATVBAHA.117.309225. Epub 2017 Jul 6.

Authors

Carlos Pérez-Sánchez¹, María Ángeles Aguirre¹, Patricia Ruiz-Limón¹, María Carmen Ábalos-Aguilera¹, Yolanda Jiménez-Gómez¹, Iván Arias-de la Rosa¹, Antonio Rodriguez-Ariza¹, Lucía Fernández-Del Río¹, José Antonio González-Reyes¹, Pedro Segui¹, Eduardo Collantes-Estévez¹, Nuria Barbarroja¹, Francisco Velasco¹, Savino Sciascia¹, Irene Cecchi¹, María José Cuadrado¹, José Manuel Villalba¹, Chary López-Pedrera²

Affiliations

¹ From the Instituto Maimónides de Investigación Biomédica de Córdoba, Córdoba, Spain (C.P.-S., M.Á.A., P.R.-L., M.C.A.-A., Y.J.-G., I.A.-d.l.R., A.R.A., P.S., E.C.-E., N.B., F.V., C.L.-P.); Unidad de Gestión Clínica Reumatología (M.Á.A., E.C.-E., C.L.-P.), Unidad de Gestión Clínica Radiología (P.S.), and Unidad de Gestión Clínica Hematología (F.V.), Hospital Universitario Reina Sofía, Córdoba, Spain; Departamento de Biología Celular, Fisiología e Inmunología, Campus de Excelencia Internacional Agroalimentario, ceiA3 (L.F.-d.R., J.A.G.-R., J.M.V.) and Departamento de Medicina (Medicina, Dermatología y Otorrinolaringología) (E.C.-E.), Universidad de Córdoba, Córdoba, Spain; Lupus Research Unit, Hospital St Thomas, London, United Kingdom (M.J.C.); and Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, University of Turin, Italy (S.S., I.C.).
² From the Instituto Maimónides de Investigación Biomédica de Córdoba, Córdoba, Spain (C.P.-S., M.Á.A., P.R.-L., M.C.A.-A., Y.J.-G., I.A.-d.l.R., A.R.A., P.S., E.C.-E., N.B., F.V., C.L.-P.); Unidad de Gestión Clínica Reumatología (M.Á.A., E.C.-E., C.L.-P.), Unidad de Gestión Clínica Radiología (P.S.), and Unidad de Gestión Clínica Hematología (F.V.), Hospital Universitario Reina Sofía, Córdoba, Spain; Departamento de Biología Celular, Fisiología e Inmunología, Campus de Excelencia Internacional Agroalimentario, ceiA3 (L.F.-d.R., J.A.G.-R., J.M.V.) and Departamento de Medicina (Medicina, Dermatología y Otorrinolaringología) (E.C.-E.), Universidad de Córdoba, Córdoba, Spain; Lupus Research Unit, Hospital St Thomas, London, United Kingdom (M.J.C.); and Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, University of Turin, Italy (S.S., I.C.). [email protected].

PMID: 28684614
DOI: 10.1161/ATVBAHA.117.309225

Abstract

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 Q₁₀ [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 Q₁₀. 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.

Keywords: antiphospholipid syndrome; extracellular traps; inflammation; oxidative stress; thrombosis; ubiquinol.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Antiphospholipid Syndrome / drug therapy*
Antiphospholipid Syndrome / physiopathology*
Cross-Over Studies
Endothelium, Vascular / physiology
Female
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Inflammation / physiopathology
Male
Middle Aged
Mitochondria / physiology
Monocytes / pathology
Oxidation-Reduction
Prospective Studies
Ubiquinone / analogs & derivatives*
Ubiquinone / therapeutic use
Vitamins / therapeutic use*

Substances

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Vitamins
Ubiquinone
coenzyme Q10

Associated data

ClinicalTrials.gov/NCT02218476