Background/Purpose:

To investigate the beneficial effects of in vivoubiquinol (Q, reduced form of CoQ10) supplementation on athero-thrombosis prevention in APS patients, through the implementation of a prospective, randomized, double-masked, placebo-controlled study.

Methods:

The study was conducted on 20 APS patients randomized to receive either Q (200 mg/day) or placebo for one month. Blood was drawn at time 0 and at the end of the treatment. Studies were performed in plasma and purified leukocytes subsets. Plasma Q levels, various prothrombotic/proinflammatory parameters, and oxidative stress biomarkers were evaluated. Differential expression of miRNAs in monocytes was also determined using Nanostring miRNA arrays and validated by real-time RT-PCR. Ultrastructural evaluation of mitochondria in isolated monocytes was performed by electron microscopy (EM). Endothelial activity analysis was performed by Laser-Doppler measurement of post ischemic reactive hyperemia. Carotid intimae media thickness (CIMT) was measured as an early atherosclerosis marker.

Results:

Seventeen out of 20 patients completed the intervention, which increased significantly plasma Q levels. Endothelial function improved notably, as shown by the amelioration in the highest perfusion value after occlusion was released, expressed as a percentage of change vs rest flow value (RF-PF). Q treatment decreased Tissue Factor (TF), IKK and IL8 protein expression levels in monocytes. A number of other proinflammatory mediators were further reduced in monocytes and neutrophils by effect of Q treatment (VEGF, CCL3, IL-1ß, IL6, and TNFα). Comparing to controls, 57 microRNAs were found significantly altered in APS patients. Among them, 26 were reversed by effect of Q treatment. Functional classification of those miRNAs showed a preponderance of target mRNAs involved in free radical scavenging, inflammatory response, cardiovascular disease, and reproductive system disease. Q supplementation produced a reduction in both the levels of peroxides and the percentage of monocytes with altered mitochondrial membrane potential (ΔΨm). EM analyses further indicated that Q treatment promoted an increase in monocytes’ mitochondrial size. Reduced monocyte TF expression after Q treatment was related to decreased peroxides levels, increased plasma Q levels, and improved endothelial function, which further correlated with IL8 levels. Eight out of 11 patients showing atheromatous plaques had also suffered at least one thrombotic recurrence. These pathologic processes were further linked to a poorer endothelial function compared to the remaining APS patients. Q effects were particularly relevant in those APS patients with pathologic CIMT and thrombotic recurrences, who showed a better response to Q treatment with improved endothelial function.

Conclusion:

Q supplementation at 200 mg/d significantly improved endothelial function, and reducedmitochondrial dysfunction, oxidative stress, and the expression of prothrombotic/proinflammatory proteins. Underlying epigenetic mechanisms seem to be involved. Our results support the potential impact of Qin the prevention of atherothrombosis in APS patients.Supported by: CTS-7940, PI12/01511, KANEKA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/in-vivo-ubiquinol-supplementation-reduces-the-pro-atherothrombotic-status-in-antiphospholipid-syndrome-patients-preliminary-results-of-a-clinical-trial/