title: Mitochondria-targeted antioxidant MitoQ10 improves endothelial function and attenuates cardiac hypertrophy.
abstract: Mitochondria are a major site of reactive oxygen species production, which may contribute to the development of cardiovascular disease. Protecting mitochondria from oxidative damage should be an effective therapeutic strategy; however, conventional antioxidants are ineffective, because they cannot penetrate the mitochondria. This study investigated the role of mitochondrial oxidative stress during development of hypertension in the stroke-prone spontaneously hypertensive rat, using the mitochondria-targeted antioxidant, MitoQ(10). Eight-week-old male stroke-prone spontaneously hypertensive rats were treated with MitoQ(10) (500 mumol/L; n=16), control compound decyltriphenylphosphonium (decylTPP; 500 mumol/L; n=8), or vehicle (n=9) in drinking water for 8 weeks. Systolic blood pressure was significantly reduced by approximately 25 mm Hg over the 8-week MitoQ(10) treatment period compared with decylTPP (F=5.94; P=0.029) or untreated controls (F=65.6; P=0.0001). MitoQ(10) treatment significantly improved thoracic aorta NO bioavailability (1.16+/-0.03 g/g; P=0.002, area under the curve) compared with both untreated controls (0.68+/-0.02 g/g) and decylTPP-treated rats (0.60+/-0.06 g/g). Cardiac hypertrophy was significantly reduced by MitoQ(10) treatment compared with untreated control and decylTPP treatment (MitoQ(10): 4.01+/-0.05 mg/g; control: 4.42+/-0.11 mg/g; and decylTPP: 4.40+/-0.09 mg/g; ANOVA P=0.002). Total MitoQ(10) content was measured in liver, heart, carotid artery, and kidney harvested from MitoQ(10)-treated rats by liquid chromatography-tandem mass spectrometry. All of the organs analyzed demonstrated detectable levels of MitoQ(10), with comparable accumulation in vascular and cardiac tissues. Administration of the mitochondria-targeted antioxidant MitoQ(10) protects against the development of hypertension, improves endothelial function, and reduces cardiac hypertrophy in young stroke-prone spontaneously hypertensive rats. MitoQ(10) provides a novel approach to attenuate mitochondrial-specific oxidative damage with the potential to become a new therapeutic intervention in human cardiovascular disease.
authors: BHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, University of Glasgow, 126 University Pl, Glasgow, G12 8TA United Kingdom.
authors: Delyth
authors: D
authors: Graham
authors: Ngan N
authors: NN
authors: Huynh
authors: Carlene A
authors: CA
authors: Hamilton
authors: Elisabeth
authors: E
authors: Beattie
authors: Robin A J
authors: RA
authors: Smith
authors: Helena M
authors: HM
authors: Cochemé
authors: Michael P
authors: MP
authors: Murphy
authors: Anna F
authors: AF
authors: Dominiczak
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000188:drug therapy* / Q000517:prevention & control; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004730:Endothelium, Vascular / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D011336:Probability; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D014451:Ubiquinone; C024989:coenzyme Q10