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

TitleAge-related endothelial dysfunction in human skeletal muscle feed arteries: The role of free radicals derived from mitochondria in the vasculature.
Publication TypeJournal Article
Year of Publication2017
AuthorsPark, S-Y, Kwon, OSung, Andtbacka, RHI, Hyngstrom, JR, Reese, V, Murphy, MP, Richardson, RS
JournalActa Physiol (Oxf)
Date Published2017 May 11
ISSN1748-1716
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 -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/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 mitochondrial-targeted antioxidants may have utility in terms of counteracting the attenuated blood flow and vascular dysfunction associated with advancing age. This article is protected by copyright. All rights reserved.

DOI10.1111/apha.12893
Alternate JournalActa Physiol (Oxf)
Citation Key10.1111/apha.12893
PubMed ID28493603