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

Autor:	Rossman MJ; 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.) matthew.rossman@colorado.edu., Santos-Parker JR; 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.)., Steward CAC; 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.)., Bispham NZ; 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.)., Cuevas LM; 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.)., Rosenberg HL; 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.)., Woodward KA; 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.)., Chonchol M; Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora (M.C., D.R.S.)., Gioscia-Ryan RA; 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.)., Murphy MP; and MRC Mitochondrial Biology Unit, Cambridge, United Kingdom (M.P.M.)., Seals DR; 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.).; Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora (M.C., D.R.S.).
Jazyk:	angličtina
Zdroj:	Hypertension (Dallas, Tex. : 1979) [Hypertension] 2018 Jun; Vol. 71 (6), pp. 1056-1063. Date of Electronic Publication: 2018 Apr 16.
DOI:	10.1161/HYPERTENSIONAHA.117.10787
Abstrakt:	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. (© 2018 American Heart Association, Inc.)
Databáze:	MEDLINE
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