Cited by 456Cardiovascular Health and Disease PreventionNitric Oxide and Endothelin EffectsMitochondrial Function and Pathology

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Chronic Supplementation With a Mitochondrial Antioxidant (MitoQ) Improves Vascular Function in Healthy Older Adults

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Rossman, Matthew J., Santos-Parker, Jessica R., Steward, Chelsea A.C., Bispham, Nina Z., Cuevas, Lauren M., Rosenberg, Hannah L., Woodward, Kayla A., Chonchol, Michel, Gioscia-Ryan, Rachel A., Murphy, Michael P., Seals, Douglas R.·2018·Hypertension

DOI 10.1161/hypertensionaha.117.10787PMC PMC5945293

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Abstract

Excess reactive oxygen species production by mitochondria is a key mechanism of age-related vascular dysfunction. Our laboratory has shown that supplementation with the mitochondrial-targeted antioxidant MitoQ improves vascular endothelial function by reducing mitochondrial reactive oxygen species and ameliorates arterial stiffening in old mice, but the effects in humans are unknown. Here, we sought to translate our preclinical findings to humans and determine the safety and efficacy of MitoQ. Twenty healthy older adults (60–79 years) with impaired endothelial function (brachial artery flow–mediated dilation <6%) underwent 6 weeks of oral supplementation with MitoQ (20 mg/d) or placebo in a randomized, placebo-controlled, double-blind, crossover design study. MitoQ was well tolerated, and plasma MitoQ was higher after the treatment versus placebo period ( P <0.05). Brachial artery flow–mediated dilation was 42% higher after MitoQ versus placebo ( P <0.05); the improvement was associated with amelioration of mitochondrial reactive oxygen species–related suppression of endothelial function (assessed as the increase in flow-mediated dilation with acute, supratherapeutic MitoQ [160 mg] administration; n=9; P <0.05). Aortic stiffness (carotid–femoral pulse wave velocity) was lower after MitoQ versus placebo ( P <0.05) in participants with elevated baseline levels (carotid–femoral pulse wave velocity >7.60 m/s; n=11). Plasma oxidized LDL (low-density lipoprotein), a marker of oxidative stress, also was lower after MitoQ versus placebo ( P <0.05). Participant characteristics, endothelium-independent dilation (sublingual nitroglycerin), and circulating markers of inflammation were not different (all P >0.1). These findings in humans extend earlier preclinical observations and suggest that MitoQ and other therapeutic strategies targeting mitochondrial reactive oxygen species may hold promise for treating age-related vascular dysfunction. Clinical Trial Registration—: URL: http://www.clinicaltrials.gov . Unique identifier: NCT02597023.

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Authors: Rossman, M. J., Santos-Parker, J. R., Steward, C. A. C., Bispham, N. Z., Cuevas, L. M., Rosenberg, H. L., Woodward, K. A., Chonchol, M., Gioscia-Ryan, R. A., Murphy, M. P., & Seals, D. R.
Affiliations: University of Colorado Boulder (US)
From the Department of Integrative Physiology, University of Colorado Boulder (M.J.R., J.R.S.-P., C.A.C.S., N.Z.B., L.M.C., H.L.R., K.A.W., R.A.G.-R., D.R.S.)
University of Colorado Anschutz (US)
MRC Mitochondrial Biology Unit (GB)
ORCID: Rossman, Matthew J.
Bispham, Nina Z.
Rosenberg, Hannah L.
Woodward, Kayla A.
Chonchol, Michel
Murphy, Michael P.
Seals, Douglas R.
Venue: Hypertension
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2018-06
Volume: 71
Issue: 6
Pages: 1056-1063
ISSN: 0194-911X (ISSN-L)
1524-4563
DOI: 10.1161/hypertensionaha.117.10787
PMC: PMC5945293
OpenAlex: W2796629168
Cited by: 456
References: 42
Citations by year: 2026: 71 · 2025: 48 · 2024: 55 · 2023: 54 · 2022: 65 · 2021: 54 · 2020: 58 · 2019: 38 · 2018: 12
FWCI: 30.51
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Hypertension (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Apollo (University of Cambridge) (submittedVersion)
Apollo
Funders: Wellcome Trust (110158/Z/15/Z, 110159/Z/ 15/Z, /Z/15/Z)
Georgia Clinical and Translational Science Alliance (UL1TR001082)
National Institutes of Health (UL1TR001082, AG000279)
University of Colorado Boulder (UL1 TR001082)
Medical Research Council (MC_UU_00015/3, MC-U105663142)
National Institute on Aging (R21AG049451, F32AG053009, T32AG000279)
National Institute of Diabetes and Digestive and Kidney Diseases (P30DK048520)
National Center for Advancing Translational Sciences
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords: MitoQ, mitochondria-targeted antioxidants, mitochondrial reactive oxygen species, endothelial function, flow-mediated dilation, arterial stiffness, pulse wave velocity, oxidative stress, oxidized LDL, aging, older adults, vascular dysfunction, dietary supplementation
MeSH terms: Aged, Antioxidants, Brachial Artery, Double-Blind Method, Endothelium, Vascular, Female, Follow-Up Studies, Humans, Male, Middle Aged, Mitochondria, Vasodilation, Reactive Oxygen Species, Oxidative Stress, Cross-Over Studies, Dietary Supplements, Vascular Stiffness, Healthy Volunteers

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Chronic Supplementation With a Mitochondrial Antioxidant (MitoQ) Improves Vascular Function in Healthy Older Adults

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