Apoptosis of myocytes and proliferation markers as prognostic factors in end-stage dilated cardiomyopathy.
BACKGROUND
The aim of the study was to evaluate the role of apoptosis, proliferation markers, volume density of interstitium, and myofibril volume fraction for the prognosis in patients with end-stage dilated cardiomyopathy (DCM).


METHODS
Endomyocardial biopsy was performed during open-heart surgery in 56 patients with end-stage DCM. Patients were divided into two groups, one group with shorter survival (24+/-9 months, mean+/-S.D.) and another group with survival of more than 7 years after operation. The TUNEL method was used for the detection of apoptosis, and immunohistochemical methods were used for the evaluation of inhibitor of apoptosis (bcl-2) and proliferation markers (PCNA and Ki-67).


RESULTS
The increased percentage of apoptotic myocytes, decreased expression of bcl-2, and decreased expression of PCNA and Ki-67 antigen was found in the group with early mortality compared to that with longer survival. Myofibril volume fraction was lower and volume density of interstitium was higher in the group with early mortality compared to that with longer survival.


CONCLUSIONS
Apoptosis, bcl-2 expression, and proliferation activity of myocytes, myofibril volume fraction, and volume density of interstitial tissue might be useful in predicting the prognosis (progressive vs. nonprogressive form) of patients with heart failure due to DCM.
Zorc
Marjeta
M
Institute of Histology and Embryology, Medical Faculty Ljubljana, University of Ljubljana, Korytkova 2, 1000, Ljubljana, Slovenia.
Vraspir-Porenta
Olga
O
Zorc-Pleskovic
Ruda
R
Radovanović
Ninoslav
N
Petrovic
Daniel
D
D000328:Adult; D000368:Aged; D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis*; D001706:Biopsy; D002311:Cardiomyopathy, Dilated / Q000401:mortality / Q000473:pathology*; D002455:Cell Division; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000473:pathology*; D011237:Predictive Value of Tests; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis
D015415:Biomarkers; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2