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Reduced nicotinamide adenine dinucleotide phosphate oxidase-derived superoxide and vascular endothelial dysfunction in human heart failure.

AbstractOBJECTIVES:
We investigated the role of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in endothelial dysfunction in human heart failure.
BACKGROUND:
Vascular endothelial dysfunction in human heart failure contributes to increased tone, exercise limitation, and dysregulation of venous capacitance and vascular volume. The NADPH oxidases (Nox) are an important source of oxidative stress, but their role in the endothelial dysfunction of human heart failure remains unknown.
METHODS:
Endothelium-dependent and -independent vasorelaxation were assessed in saphenous vein segments obtained from consecutive patients with heart failure (n = 19) or normal left ventricular function (control; n = 35) undergoing coronary artery bypass graft. Saphenous vein superoxide production was measured by lucigenin-enhanced chemiluminescence and messenger ribonucleic acid expression of relevant transcripts quantified by real-time polymerase chain reaction.
RESULTS:
Heart failure patients had significantly worse endothelial function than control subjects (15.2 +/- 3% vs. 40.5 +/- 8.4% relative relaxation; p < 0.05), elevated C-reactive protein (CRP) levels (8.6 +/- 2.7 mg/l vs. 2.6 +/- 0.4 mg/l; p < 0.05), over 2-fold higher NADPH-dependent superoxide generation (p < 0.05), and significantly higher expression of the Nox4 isoform and regulatory subunit p67phox. Superoxide levels were positively correlated with New York Heart Association functional class (r = 0.684; p < 0.05) and CRP (r = 0.501; p < 0.005; n = 32).
CONCLUSIONS:
Venous endothelial dysfunction in human heart failure is associated with increased Nox-derived superoxide generation. Inflammatory mechanisms may be involved in the increased reactive oxygen species generation.
AuthorsRafał Dworakowski, Simon Walker, Aziz Momin, Jatin Desai, Ahmed El-Gamel, Olaf Wendler, Mark T Kearney, Ajay M Shah
JournalJournal of the American College of Cardiology (J Am Coll Cardiol) Vol. 51 Issue 14 Pg. 1349-56 (Apr 8 2008) ISSN: 1558-3597 [Electronic] United States
PMID18387435 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Biomarkers
  • Reactive Oxygen Species
  • Superoxides
  • C-Reactive Protein
  • NADPH Oxidase
  • Nitrous Oxide
Topics
  • Aged
  • Biomarkers (metabolism)
  • C-Reactive Protein (metabolism)
  • Cardiovascular Diseases (metabolism, physiopathology)
  • Case-Control Studies
  • Endothelium, Vascular (physiopathology)
  • Exercise Tolerance
  • Female
  • Heart Failure (metabolism, physiopathology)
  • Humans
  • Inflammation (metabolism)
  • Male
  • Middle Aged
  • NADPH Oxidase (metabolism)
  • Nitrous Oxide (metabolism)
  • Oxidative Stress
  • Reactive Oxygen Species (metabolism)
  • Saphenous Vein
  • Superoxides (metabolism)

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