Elevated levels of reactive oxygen species in heart failure patients: role for increased mononuclear NADPH oxidase expression (1153.9)

Although heart failure (HF) patients exhibit elevated levels of ROS, the sources and mechanisms contributing to the increase in ROS remain unclear. Recent work has shown that peripheral blood mononuclear cells (PBMCs) are a major source of NADPH oxidase-derived superoxide (O2●-) production. Therefore, we measured systemic ROS, O2●-, and expression of NADPH oxidase and its potential activators, angiotensin II type 1 receptors (AT1R) and Rho Kinase (ROCK) 1, in PBMCs from 6 HF (ejection fraction 22±4%) and 6 age-matched healthy controls. Total ROS and O2●- levels were measured in blood using electron paramagnetic resonance spectroscopy. Protein expression of NADPH oxidase subunits (gp91phox, p22phox, p47phox and p67phox), AT1R and ROCK1 were assessed from PBMCs using western blot. Total ROS and O2●- levels were elevated in blood from HF patients compared to controls (P<0.05). HF patients showed augmented protein expression of all NADPH oxidase subunits (e.g. 4±1 fold increase in gp91phox; P<0.05 vs. control...