Abstract | OBJECTIVES: 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:
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Authors | Rafał Dworakowski, Simon Walker, Aziz Momin, Jatin Desai, Ahmed El-Gamel, Olaf Wendler, Mark T Kearney, Ajay M Shah |
Journal | Journal of the American College of Cardiology
(J Am Coll Cardiol)
Vol. 51
Issue 14
Pg. 1349-56
(Apr 08 2008)
ISSN: 1558-3597 [Electronic] United States |
PMID | 18387435
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers
- Reactive Oxygen Species
- Superoxides
- C-Reactive Protein
- NADPH Oxidases
- Nitrous Oxide
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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 Oxidases
(metabolism)
- Nitrous Oxide
(metabolism)
- Oxidative Stress
- Reactive Oxygen Species
(metabolism)
- Saphenous Vein
- Superoxides
(metabolism)
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