Mitochondria-targeted antioxidant MitoQ(10) improves endothelial function and attenuates cardiac hypertrophy

Graham, D., Huynh, N.N., Hamilton, C.A., Beattie, E.C., Smith, R.A.J., Cocheme, H.M., Murphy, M.P. and Dominiczak, A.F. (2009) Mitochondria-targeted antioxidant MitoQ(10) improves endothelial function and attenuates cardiac hypertrophy. Hypertension, 54(2), 322-U233. (doi: 10.1161/HYPERTENSIONAHA.109.130351)

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, MitoQ10. Eight-week–old male stroke-prone spontaneously hypertensive rats were treated with MitoQ10 (500 μmol/L; n=16), control compound decyltriphenylphosphonium (decylTPP; 500 μmol/L; n=8), or vehicle (n=9) in drinking water for 8 weeks. Systolic blood pressure was significantly reduced by ≈25 mm Hg over the 8-week MitoQ10 treatment period compared with decylTPP (F=5.94; P=0.029) or untreated controls (F=65.6; P=0.0001). MitoQ10 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 MitoQ10 treatment compared with untreated control and decylTPP treatment (MitoQ10: 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 MitoQ10 content was measured in liver, heart, carotid artery, and kidney harvested from MitoQ10-treated rats by liquid chromatography-tandem mass spectrometry. All of the organs analyzed demonstrated detectable levels of MitoQ10, with comparable accumulation in vascular and cardiac tissues. Administration of the mitochondria-targeted antioxidant MitoQ10 protects against the development of hypertension, improves endothelial function, and reduces cardiac hypertrophy in young stroke-prone spontaneously hypertensive rats. MitoQ10 provides a novel approach to attenuate mitochondrial-specific oxidative damage with the potential to become a new therapeutic intervention in human cardiovascular disease.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Graham, Dr Delyth and Hamilton, Dr Carlene and Dominiczak, Professor Anna and Beattie, Mrs Elisabeth
• Authors: Graham, D., Huynh, N.N., Hamilton, C.A., Beattie, E.C., Smith, R.A.J., Cocheme, H.M., Murphy, M.P., and Dominiczak, A.F.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Hypertension
• Publisher: American Heart Association
• ISSN: 0194-911X
• Published Online: 06 July 2009