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dc.contributor.authorRossman, Matthew Jen
dc.contributor.authorSantos-Parker, Jessica Ren
dc.contributor.authorSteward, Chelsea ACen
dc.contributor.authorBispham, Nina Zen
dc.contributor.authorCuevas, Lauren Men
dc.contributor.authorRosenberg, Hannah Len
dc.contributor.authorWoodward, Kayla Aen
dc.contributor.authorChonchol, Michelen
dc.contributor.authorGioscia-Ryan, Rachel Aen
dc.contributor.authorMurphy, Mikeen
dc.contributor.authorSeals, Douglas Ren
dc.date.accessioned2018-09-05T10:57:22Z
dc.date.available2018-09-05T10:57:22Z
dc.date.issued2018-06en
dc.identifier.issn0194-911X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/279101
dc.description.abstractExcess 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.
dc.description.sponsorshipThis work was supported by National Institutes of Health (NIH) awards AG049451, AG000279, AG053009, Colorado CTSA UL1 TR001082, and an industry contract with MitoQ Limited (MitoQ Limited provided MitoQ and some financial support). M.P. Murphy is supported by UK MRC MC_U105663142 and as a Wellcome Trust Investigator (110159/Z/15/Z).
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherWolters Kluwer Health
dc.subjectBrachial Arteryen
dc.subjectEndothelium, Vascularen
dc.subjectMitochondriaen
dc.subjectHumansen
dc.subjectReactive Oxygen Speciesen
dc.subjectAntioxidantsen
dc.subjectFollow-Up Studiesen
dc.subjectCross-Over Studiesen
dc.subjectDouble-Blind Methoden
dc.subjectOxidative Stressen
dc.subjectVasodilationen
dc.subjectDietary Supplementsen
dc.subjectAgeden
dc.subjectMiddle Ageden
dc.subjectFemaleen
dc.subjectMaleen
dc.subjectVascular Stiffnessen
dc.subjectHealthy Volunteersen
dc.titleChronic Supplementation With a Mitochondrial Antioxidant (MitoQ) Improves Vascular Function in Healthy Older Adults.en
dc.typeArticle
prism.endingPage1063
prism.issueIdentifier6en
prism.publicationDate2018en
prism.publicationNameHypertension (Dallas, Tex. : 1979)en
prism.startingPage1056
prism.volume71en
dc.identifier.doi10.17863/CAM.26481
dcterms.dateAccepted2018-02-28en
rioxxterms.versionofrecord10.1161/hypertensionaha.117.10787en
rioxxterms.versionAM*
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2018-06en
dc.contributor.orcidMurphy, Michael [0000-0003-1115-9618]
dc.identifier.eissn1524-4563
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_U105663142)
pubs.funder-project-idMRC (MC_UU_00015/3)
pubs.funder-project-idWellcome Trust (110159/Z/15/Z)
rioxxterms.freetoread.startdate2018-10-16


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