© 2002 by European Society of Cardiology
Copyright © 2001, European Society of Cardiology
Reversible activation of nuclear factor-
B in human end-stage heart failure after left ventricular mechanical support
aThe Gerhard-Domagk-Institute of Pathology, University of Münster, Domagkstrasse 17, 48149 Münster, Germany
bThe Institute of Arteriosclerosis Research, University of Münster, Domagkstrasse 3, 48149 Münster, Germany
cDepartment of Cardio-thoracic Surgery, University of Münster, Albert-Schweitzer Strasse 33, 48149 Münster, Germany
dThe Heart Failure Center, Columbia University, New York, NY, USA
eDepartment of Internal Medicine, Aoto Hospital, Jikei University, Tokyo, Japan
fDepartment of Cardiology and Angiology, University of Münster, Albert-Schweitzer Strasse 33, 48149 Münster, Germany
* Corresponding author. Tel.: +49-251-835-5446; fax: +49-251-835-5460 baba{at}uni-muenster.de
Objective: Left ventricular assist devices (LVAD) have been used to ‘bridge’ patients with end-stage heart failure to transplantation. Although several reports have suggested that the native ventricular function recovers after long-term LVAD support, a process called ‘reverse remodeling’, the underlying biological mechanisms are still unknown. As the transcription factor nuclear factor-
B (NF-B) has been shown to be active in the failing human heart, we examined whether its activity is altered under LVAD support, and may thus contribute to the dynamic process of ‘reverse remodeling’. Methods: The activity of NF-B was studied in 16 patients with end-stage heart failure (eight with dilated cardiomyopathy, six with ischemic heart disease, one with myocarditis, and one with congenital heart disease) before and after LVAD support by immunohistochemistry using an antibody against active NF-B. Gel-shifts for NF-B DNA-binding activity were performed with paired human myocardial tissue from four patients. The mean cardiomyocyte diameter before and after mechanical unloading was measured with an image analyzer system. Results: 15 patients out of 16 showed a significant decrease in the number of NF-B positive cardiomyocyte nuclei after LVAD support in the left ventricular myocardium. The NF-B DNA-binding activity also decreased after LVAD support as measured by gel-shift analysis. While the number of positive cardiomyocytes was significantly higher in the subendocardium than in the subepicardium at the time of LVAD implantation, this difference was no longer present at the time of LVAD explantation. The diameter of cardiomyocytes in the left ventricle decreased significantly as a parameter of structural reverse remodeling. Conclusion: LVAD support decreases the extent of NF-B activation in failing human hearts, suggesting that NF-B may be involved in the process of ‘reverse remodeling’.
KEYWORDS Heart failure; Hypertrophy; Myocytes; Remodeling; Signal transduction
1 The first two authors have contributed equally to this work.
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