Acute mitochondrial antioxidant intake improves endothelial function, antioxidant enzyme activity, and exercise tolerance in patients with peripheral artery disease

Abstract

Peripheral artery disease (PAD) is a manifestation of atherosclerosis in the leg arteries, which causes claudication. This may be in part due to vascular mitochondrial dysfunction and excessive reactive oxygen species (ROS) production. A mitochondrial-targeted antioxidant (MitoQ) has been shown to improve vascular mitochondrial function which, in turn, led to improved vascular function in older adults and animal models. However, the roles of vascular mitochondria in vascular function including endothelial function and arterial stiffness in patients with PAD are unknown, therefore, by utilizing acute MitoQ intake, this study examined the roles of vascular mitochondria in endothelial function, arterial stiffness, exercise tolerance, and skeletal muscle function in patients with PAD. 11 patients with PAD received either MitoQ or placebo in a randomized crossover design. At each visit, blood samples, brachial and popliteal artery flow-mediated dilation (FMD), peripheral and central pulse-wave velocity (PWV), blood pressure (BP), maximal walking capacity, time to claudication (COT), and oxygen utility capacity were measured pre-and-post MitoQ and placebo. There were significant group by time interactions (p<0.05) for brachial and popliteal FMD which both increased (Δ2.6% and Δ3.3%, respectively), and increases superoxide dismutase (Δ0.03 U/mL), maximal walking time (Δ73.8 s), maximal walking distance (Δ49.3 m) and COT (Δ44.2 s). There were no changes in resting heart rate, BP, malondialdehyde, total antioxidant capacity, PWV, or oxygen utility capacity (p>0.05). MitoQ intake may be an effective strategy for targeting the vascular mitochondrial environment, which may be useful for restoring endothelial function, leg pain, and walking time in patients with PAD.

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“…Irreparable mitochondrial damage will release pro-apoptotic proteins into the cytoplasm and initiate the mitochondria-mediated death pathway. Endothelial mitochondrial dysfunction has been linked to several diseases such as diabetes-induced microvascular injury, cerebral ischemia-reperfusion injury (Zhang et al, 2020), nephropathy (Zhai et al, 2020), peripheral artery disease (Park et al, 2020), and pulmonary artery hypertension (Wang et al, 2020). Many researches have observed the role of mitochondrial damage in triggering endothelial dysfunction upon ox-LDL treatment (Li et al, 2018, Li et al, 2020Yuan et al, 2019;Xie et al, 2020), suggesting an urgent need for therapies that protect endothelial mitochondria in order to reduce atherosclerosis development.…”

Patient Endothelial Colony-Forming Cells to Model Coronary Artery Disease Susceptibility and Unravel the Role of Dysregulated Mitochondrial Redox Signalling

“…There were additional benefits to hyperglycaemia and hepatic steatosis, as well as on multiple metabolically relevant lipid species. The usefulness of MitoQ treatment has not yet been investigated in patients with atherosclerosis, but it has recently been proven to significantly increase the endothelial function of aged persons and patients with peripheral artery disease [38,39], suggesting it has promising therapeutic potential.…”

Oxidative Stress, Mitochondrial Function and Adaptation to Exercise: New Perspectives in Nutrition

“…Park et al [146] reported that the acute oral intake of MitoQ (80 mg) improved maximal walking capacity and postponed the onset of limping in individuals with peripheral artery disease. The authors also observed increasing vascular endothelial function and SOD.…”