Peripheral blood mononuclear cell mitochondrial bioenergetics are related to vascular endothelial function in young...

The use of peripheral blood mononuclear cells (PBMCs) in cardiovascular research is increasingly common. However, little is known regarding potential age-related changes in mitochondrial bioenergetics and oxidative stress in PBMCs, or whether such changes relate to endothelial function. We assessed mitochondrial bioenergetics and antioxidant buffering capacity (AoxBC) capacity in PBMCs from young (n = 18; 21 ± 2 yr) and older (n = 17, 66 ± 4 yr) adults. High-resolution respirometry and fluorometry measured mitochondrial respiration rate (JO₂) and membrane potential (Δψm), respectively, in response to substrate provision (pyruvate, glutamate, malate, and succinate; PGMS) and a bioenergetic creatine kinase (CK) clamp at physiological ATP:ADP ratios (PCr1, PCr2, and PCr3). MtROS emission was measured as hydrogen peroxide (H₂O₂) emission, and H₂O₂ production was quantified using inhibitors of glutathione reductase and thioredoxin/peroxiredoxin. AoxBC was calculated as the percentage of H₂O₂ produced but not emitted. Endothelial function was assessed through flow-mediated dilation (FMD). JO₂ was similar between groups at baseline (P = 0.08) and lower energetic states (PCr2, PCr3; P ≥ 0.09), but was lower in older adults at higher energetic states (PCr1: 14.05 ± 2.11 vs. 12.03 ± 2.98 pmol·s^-1·10⁶ cells^-1, P = 0.03; PGMS: 20.61 ± 2.11 vs. 16.58 ± 3.56 pmol·s^-1·10⁶ cells^-1; P = 0.0009). Δψm was hypopolarized in older compared with young adults at all energetic states (P ≤ 0.003). Although there were no statistical differences in H₂O₂ emission (P = 0.43) or production (P = 0.18), AoxBC was lower in older adults (52.59 ± 15.44% vs. 63.49 ± 10.30%; P = 0.03). Age-related changes in JO₂ (PGMS, P = 0.02) and Δψm (PGMS, P = 0.0008; PCr2, P = 0.04; PCr3, P = 0.02) were related to FMD. These data demonstrate associations between altered PBMC mitochondrial bioenergetics and age-related vascular endothelial dysfunction.NEW & NOTEWORTHY The use of peripheral blood mononuclear cells (PBMCs) is increasingly common in cardiovascular research. However, relatively little is known regarding potential age-related changes in PBMC mitochondrial bioenergetics and oxidative stress, or whether age-related changes are related to endothelial (dys)function. We demonstrate altered mitochondrial bioenergetics (oxygen consumption rates and membrane potential) and antioxidant buffering capacity in PBMCs from older compared with young adults. We additionally demonstrate associations between mitochondrial bioenergetics and endothelial function (brachial-artery flow-mediated dilation).