1. Age-related endothelial dysfunction in human skeletal muscle feed arteries: the role of free radicals derived from mitochondria in the vasculature
- Author
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Park, S-Y, Kwon, OS, Andtbacka, RHI, Hyngstrom, JR, Reese, V, Murphy, MP, Richardson, RS, Murphy, Mike [0000-0003-1115-9618], and Apollo - University of Cambridge Repository
- Subjects
Adult ,Male ,Aging ,Free Radicals ,Ubiquinone ,nitric oxide bioavailability ,Arteries ,MitoQ ,Antioxidants ,Mitochondria ,Vasodilation ,Organophosphorus Compounds ,ageing ,endothelial-dependent vasodilation ,mitochondria-targeted antioxidant ,Humans ,Female ,Endothelium, Vascular ,Muscle, Skeletal ,Aged - Abstract
AIM: This study sought to determine the role of free radicals derived from mitochondria in the vasculature in the recognized age-related endothelial dysfunction of human skeletal muscle feed arteries (SMFAs). METHODS: A total of 44 SMFAs were studied with and without acute exposure to the mitochondria-targeted antioxidant MitoQ and nitric oxide synthase (NOS) blockade. The relative abundance of proteins from the electron transport chain, phosphorylated (p-) to endothelial (e) NOS ratio, manganese superoxide dismutase (MnSOD) and the mitochondria-derived superoxide (O2-) levels were assessed in SMFA. Endothelium-dependent and endothelium-independent SMFA vasodilation was assessed in response to flow-induced shear stress, acetylcholine (ACh) and sodium nitroprusside (SNP). RESULTS: MitoQ restored endothelium-dependent vasodilation in the old to that of the young when stimulated by both flow (young: 68 ± 5; old: 25 ± 7; old + MitoQ 65 ± 9%) and ACh (young: 97 ± 4; old: 59 ± 10; old + MitoQ: 98 ± 5%), but did not alter the initially uncompromised, endothelium-independent vasodilation (SNP). Compared to the young, MitoQ in the old diminished the initially elevated mitochondria-derived O2- levels and appeared to attenuate the breakdown of MnSOD. Furthermore, MitoQ increased the ratio of p-eNOS to NOS and the restoration of endothelium-dependent vasodilation in the old by MitoQ was ablated by NOS blockade. CONCLUSION: This study demonstrated that MitoQ reverses age-related vascular dysfunction by what appears to be an NO-dependent mechanism in human SMFAs. These findings suggest that mitochondria-targeted antioxidants may have utility in terms of counteracting the attenuated blood flow and vascular dysfunction associated with advancing age.
- Published
- 2018