Relationship between tumor necrosis factor-alpha production and oxidative stress in the failing hearts of patients with dilated cardiomyopathy.

Abstract

OBJECTIVES:

This study evaluated oxidative stress in the failing ventricle in patients with dilated cardiomyopathy (DCM).

BACKGROUND:

Oxidative stress appears to increase in the failing myocardium and may contribute to ventricular dysfunction in patients with DCM. Tumor necrosis factor-alpha (TNF-alpha), which is expressed in the failing heart, may stimulate oxidative stress.

METHODS:

We measured plasma oxidized low density lipoprotein (oxLDL) by sandwich enzyme-linked immunosorbent assay using specific antibodies against oxLDL in the aortic root (AO) and the coronary sinus (CS) in control subjects (n = 8) and in 22 patients with DCM and mild congestive heart failure. We also measured the plasma levels of TNF-alpha and angiotensin II.

RESULTS:

There was no difference in oxLDL between the AO and CS in control subjects. In contrast, plasma oxLDL was significantly higher in the CS than the AO in patients with DCM, suggesting that the transcardiac gradient ofoxLDL reflects oxidative stress in the failing heart in these patients. Plasma TNF-alpha levels were significantly higher in the CS than the AO with a significant positive correlation of the transcardiac gradient of TNF-alpha and the transcardiac gradient of oxLDL. Moreover, a significant negative correlation existed between the transcardiac gradient of oxLDL and left ventricular ejection fraction. The transcardiac gradient of plasma oxLDL was significantly lower in 6 patients who received carvedilol than in 16 patients who did not receive carvedilol.

CONCLUSIONS:

These findings indicate that the transcardiac gradient of oxLDL may be a marker of oxidative stress in the heart and that left ventricular dysfunction may be partly due to the oxidative stress in patients with DCM. In addition, TNF-alpha may stimulate oxidative stress in the failing heart in patients with DCM.

• Authors: T Tsutamoto, A Wada, T Matsumoto, K Maeda, N Mabuchi, M Hayashi, T Tsutsui, M Ohnishi, M Sawaki, M Fujii, T Matsumoto, T Yamamoto, H Horie, Y Sugimoto, M Kinoshita
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 37 Issue 8 Pg. 2086-92 (Jun 15 2001) ISSN: 0735-1097 [Print] United States
• PMID: 11419892 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic beta-Antagonists
• Carbazoles
• Lipoproteins, LDL
• Propanolamines
• Thiobarbituric Acid Reactive Substances
• Tumor Necrosis Factor-alpha
• Carvedilol

Topics

• Adolescent
• Adrenergic beta-Antagonists (therapeutic use)
• Adult
• Aged
• Carbazoles (therapeutic use)
• Cardiomyopathy, Dilated (drug therapy, physiopathology)
• Carvedilol
• Enzyme-Linked Immunosorbent Assay
• Female
• Hemodynamics
• Humans
• Lipoproteins, LDL (analysis)
• Male
• Middle Aged
• Oxidative Stress (physiology)
• Propanolamines (therapeutic use)
• Thiobarbituric Acid Reactive Substances
• Tumor Necrosis Factor-alpha (biosynthesis)
• Ventricular Dysfunction, Left (physiopathology)