Mitochondria-targeted antioxidant MitoQ10 improves endothelial function and attenuates cardiac hypertrophy.

TitleMitochondria-targeted antioxidant MitoQ10 improves endothelial function and attenuates cardiac hypertrophy.
Publication TypeJournal Article
Year of Publication2009
AuthorsGraham, D, Huynh, NN, Hamilton, CA, Beattie, E, Smith, RAJ, Cochemé, HM, Murphy, MP, Dominiczak, AF
JournalHypertension
Volume54
Issue2
Pagination322-8
Date Published2009 Aug
ISSN1524-4563
KeywordsAnalysis of Variance, Animals, Antioxidants, Blood Pressure, Cardiomegaly, Disease Models, Animal, Drug Delivery Systems, Endothelium, Vascular, Hypertension, Male, Membrane Potential, Mitochondrial, Mitochondria, Oxidative Stress, Probability, Random Allocation, Rats, Rats, Inbred SHR, Risk Factors, Sensitivity and Specificity, Ubiquinone
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.

DOI10.1161/HYPERTENSIONAHA.109.130351
Alternate JournalHypertension
Citation Key10.1161/HYPERTENSIONAHA.109.130351
PubMed ID19581509
Grant ListMC_U105663142 / / Medical Research Council / United Kingdom
/ / British Heart Foundation / United Kingdom
/ / Wellcome Trust / United Kingdom