Reduced Nicotinamide Adenine Dinucleotide Phosphate Oxidase-Derived Superoxide and Vascular Endothelial Dysfunction in Human Heart Failure
Rafa Dworakowski, MD, PhD*,
Simon Walker*,
Aziz Momin, FRCS*,
Jatin Desai, FRCS*,
Ahmed El-Gamel, FRCS*,
Olaf Wendler, MD, PhD*,
Mark T. Kearney, MD, FRCP and
Ajay M. Shah, MD, FMedSci*,*
* Cardiovascular Division, King’s College London School of Medicine, London, United Kingdom
Leeds Institute for Genetics, Health and Therapeuticss, University of Leeds, Leeds, United Kingdom.
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Figure 1 Plasma Levels of Inflammatory Markers CRP, IL-6, and TNF- in Subjects With or Without Heart Failure
(A) C-reactive protein (CRP) levels in control versus heart failure groups; *p < 0.05 by Mann-Whitney test. (B) CRP levels by New York Heart Association (NYHA) functional class. The linear regression was adjusted for diabetes and renal failure. (C) Interleukin (IL)-6 levels. (D) Tumor necrosis factor (TNF)- levels.
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Figure 2 Vasomotor Function in Saphenous Vein Segments From Control and Heart Failure Groups
(A) Mean concentration-response relationship for acetylcholine (ACh). (B) Mean concentration-response relationship for sodium nitroprusside (SNP). (C) Relative endothelial-dependent relaxation (maximum response to ACh normalized by the maximal response to SNP). *p < 0.05 by Mann-Whitney test.
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Figure 3 Superoxide Production by Human Saphenous Veins From Patients With and Without Heart Failure
(A) Superoxide production by lucigenin-enhanced chemiluminescence. *p < 0.05 by Mann-Whitney test. (B) Relationship between superoxide and New York Heart Association (NYHA) functional class using a linear regression model adjusted for diabetes and renal failure. *p < 0.05. (C) Effect of various inhibitors on superoxide production in the control and heart failure groups. *p < 0.05 by analysis of variance followed by Scheffe test, to test for differences among interventions in either the control group or the heart failure group. DPI = diphenyleneiodonium; L-NAME = NG-nitro-L-arginine methyl ester. (D) Relationship between superoxide and C-reactive protein (CRP) levels; Pearson correlation: r = 0.501; p < 0.05.
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Figure 4 Expression of Nox Isoforms by Real-Time Polymerase Chain Reaction in Human Saphenous Veins From Patients With and Without Heart Failure
(A) Nox2 expression; (B) Nox4 expression; (C) p47phox expression; (D) p67phox expression. *p < 0.05 by unpaired Student t test. mRNA = messenger ribonucleic acid; Nox = nicotinamide adenine dinucleotide phosphate oxidase.
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