Diabetes mellitus is associated with impaired mitochondrial oxidative phosphorylation system and increased oxidative stress in human atria

Background The diabetic heart exhibits a reduced tolerance to metabolic stress resulting in higher susceptibility to injury and heart failure yet the underlying mechnisms of reduced tolerance are not fully defined. We hypothesized that impairment in oxidative phosphorylation (OXPHOS) and increased oxidative stress can contribute to enhanced myocardial vulnerability to injury in the diabetic heart. Methods Right atrial appendage tissue from well-matched patients with diabetes mellitus (DM) (n=11) and without DM (nDM) (n=20) undergoing cardiac bypass surgery was immediately frozen in liquid nitrogen and stored at -80ºC. Enzymatic activity of mitochondrial OXPHOS complexes I-V was assessed in tissue homogenates spectrophotometrically. The level of 4-hydroxynonenal (4-HNE) was measured by the OxiSelect HNE adduct competitive ELISA commercial kit. Results When compared to nDM, DM had variable but statistically significant reduction in the activity of OXPHOS complexes I, II, IV and V (Panel A). This correlated with enhanced level of 4-HNE, a marker of oxidative stress, in patients with DM (Panel B). Conclusions Impairment of atrial mitochondrial energetics and increased oxidative stress in patients with DM could contribute to myocardial dysfunction and enhanced susceptibility of diabetic heart to injury