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Acta Physiol (Oxf). 2018 Jan;222(1). doi: 10.1111/apha.12893. Epub 2017 Jun 8.

Age-related endothelial dysfunction in human skeletal muscle feed arteries: the role of free radicals derived from mitochondria in the vasculature.

Author information

1
The School of Health and Kinesiology, University of Nebraska- Omaha, Omaha, NE, USA.
2
Geriatric Research, Education, and Clinical Center, George E. Whalen VA Medical Center, Salt Lake City, UT, USA.
3
Department of Internal Medicine, Division of Geriatrics, University of Utah, Salt Lake City, UT, USA.
4
Department of Surgery, Huntsman Cancer Hospital, University of Utah, Salt Lake City, UT, USA.
5
MRC Mitochondrial Biology Unit, Cambridge Biomedical Campus, Cambridge, UK.
6
Department of Exercise and Sport Science, University of Utah, Salt Lake City, UT, USA.
7
Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT, USA.

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.

KEYWORDS:

MitoQ; ageing; endothelial-dependent vasodilation; mitochondria-targeted antioxidant; nitric oxide bioavailability

PMID:
28493603
DOI:
10.1111/apha.12893

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