Premium
Elevated levels of reactive oxygen species in heart failure patients: role for increased mononuclear NADPH oxidase expression (1153.9)
Author(s) -
Deo Shekhar,
Zimmerman Matthew,
Zucker Irving,
Fadel Paul
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1153.9
Subject(s) - nadph oxidase , reactive oxygen species , western blot , peripheral blood mononuclear cell , chemistry , superoxide , medicine , superoxide dismutase , oxidative stress , angiotensin ii , endocrinology , microbiology and biotechnology , receptor , biology , biochemistry , enzyme , in vitro , gene
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 (O 2 ●‐ ) production. Therefore, we measured systemic ROS, O 2 ●‐ , and expression of NADPH oxidase and its potential activators, angiotensin II type 1 receptors (AT 1 R) and Rho Kinase (ROCK) 1, in PBMCs from 6 HF (ejection fraction 22±4%) and 6 age‐matched healthy controls. Total ROS and O 2 ●‐ levels were measured in blood using electron paramagnetic resonance spectroscopy. Protein expression of NADPH oxidase subunits (gp91 phox , p22 phox , p47 phox and p67 phox ), AT 1 R and ROCK1 were assessed from PBMCs using western blot. Total ROS and O 2 ●‐ 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 gp91 phox ; P <0.05 vs. control). ROCK1 protein expression was also greater in HF patients (3±1 fold; P <0.05 vs. control), whereas AT 1 R tended to be higher (2±1 fold; P =0.13 vs. control). These preliminary findings suggest that PBMC‐derived NADPH oxidase expression is up‐regulated in HF patients and may contribute to the elevated levels of ROS, including O 2 ●‐ , through a ROCK1 and/or AT 1 R dependent mechanism. Grant Funding Source : Supported by NIH RO1 HL 038690‐22