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J Am Coll Cardiol, 2002; 40:1097-1103 © 2002 by the American College of Cardiology Foundation |



* Cardiovascular Center, Aalst, Belgium
Department of Cardiology, Imelda Ziekenhuis, Bonheiden, Belgium
HistoGeneX, Edegem, Belgium
Department of Pathology, Middelheim Hospital, Antwerp, Belgium
Manuscript received November 26, 2001; revised manuscript received April 11, 2002, accepted June 18, 2002.
* Reprint requests and correspondence: Dr. Jozef Bartunek, Cardiovascular Center, OLV Ziekenhuis, Moorselbaan 164, 9 300 Aalst, Belgium.
jozef.bartunek{at}olvz-aalst.be
OBJECTIVES: The study investigated the expression and relationship of deoxyribonucleic acid (DNA) repair enzymes with hemodynamic and nitric oxide (NO)-mediated stress in the failing myocardium.
BACKGROUND: The role of apoptosis in human heart failure is controversial. Experimental studies suggested that NO-mediated stress modulates apoptosis of the cardiac myocytes. Of note, DNA repair enzymes such as redox factor/apurinic/apyridimine endonuclease Ref-1 protein, proliferative cell nuclear antigen (PCNA), the poly (ADP-ribose) polymerase (PARP), and DNA-protein kinase (DNA-PK) determine the cell fate after the DNA damage.
METHODS: Left ventricular (LV) endomyocardial biopsies from 23 patients with dilated cardiomyopathy were analyzed by immunohistochemistry.
RESULTS: Terminal deoxynucleotidyltransferase-mediated biotin-dUTP nick-end labeling (TUNEL) or cleaved caspase-3 and cleaved PARP could not be detected. The number of Ref-1-positive myocytes tended to be higher in patients with LV ejection fraction (EF)
35% versus LV EF >35% (21.23 ± 4.8% vs. 13.8 ± 5.8%, p = 0.1). The PCNA (7.1 ± 2.8% vs. 0.9 ± 0.6%, p = 0.05) and DNA-PK expressions (39.5 ± 5.4% vs. 8.6 ± 5.5%, p < 0.01) were higher in patients with LVEF
35% vs. LVEF >35%. The PCNA, Ref-1, and DNA-PK expression correlated with the LV end-systolic wall stress (r = 0.61, p < 0.01; r = 0.52, p < 0.01; and r = 0.73, p < 0.001, respectively). In addition, the PCNA and DNA-PK expression correlated with inducible NO synthase (r = 0.41, p = 0.05, and r = 0.53, p < 0.01, respectively).
CONCLUSIONS: In this study, apoptosis could not be detected in the failing myocardium owing to idiopathic dilated cardiomyopathy. In contrast, failing myocardium was characterized by active DNA repair that was associated with elevated LV wall stress and activation of the inducible NO synthase.
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