Acute effects of MitoQ on vascular endothelial function are influenced by cardiorespiratory fitness and baseline FMD in middle-aged and older adults.

Abstract

A key mechanism promoting vascular endothelial dysfunction is mitochondrial-derived reactive oxygen species (mtROS). Aerobic exercise preserves endothelial function in preclinical models by lowering mtROS. However, the effects of mtROS on endothelial function in exercising and non-exercising adults is limited. In a double-blind, randomized, placebo-controlled crossover study design 23 (10M/13 F, age 62.1 ± 11.5 years) middle-aged and older (MA/O, ≥45 years) adults were divided into two groups: exercisers (EX, n=11) and non-exercisers (NEX, n=12). All participants had endothelial function (brachial artery flow-mediated dilatation, FMDBA) measured before and ∼1h after mitoquinone mesylate (MitoQ) (single dose, 80mg) and placebo supplementation. A two-way repeated measures ANOVA was used to determine the effects of MitoQ and placebo on FMDBA. Pearson correlations assessed the association between the change in FMDBA with MitoQ and baseline FMDBA and cardiorespiratory fitness (CRF). Compared with placebo, MitoQ increased FMDBA in NEX by + 2.1% (MitoQ pre: 4.9 ± 0.4 vs. post: 7.0 ± 0.4 %, P=0.004, interaction) but not in EX (P=0.695, interaction). MitoQ also increased endothelial function in adults with a FMDBA <6% (P < 0.0001, interaction) but not >6% (P=0.855, interaction). Baseline FMDBA and CRF were correlated (r=0.44, P=0.037), whereas the change in FMDBA with MitoQ was inversely correlated with CRF (r=-0.66, P < 0.001) and baseline FMDBA (r=-0.73, P < 0.0001). The relationship between the change in FMDBA and baseline FMDBA remained correlated after adjusting for CRF (r=-0.55, P=0.007). These data demonstrate that MitoQ acutely improves FMDBA in NEX and EX adults who have a baseline FMDBA <6%. KEY POINTS: A key age-related change contributing to increased cardiovascular disease (CVD) risk is vascular endothelial dysfunction due to increased mitochondrial-derived reactive oxygen species (mtROS). Aerobic exercise preserves endothelial function via suppression of mtROS in preclinical models but the evidence in humans is limited. In the present study, a single dose of the mitochondria-targeted antioxidant, mitoquinone mesylate (MitoQ), increases endothelial function in non-exercisers with lower cardiorespiratory fitness (CRF) but not in exercisers with higher CRF. The acute effects of MitoQ on endothelial function in middle-aged and older adults (MA/O) are influenced by baseline endothelial function independent of CRF. These data provide initial evidence that the acute MitoQ-enhancing effects on endothelial function in MA/O adults are influenced, in part, via CRF and baseline endothelial function.