O. Akyurek et al., Association between the severity of heart failure and the susceptibility of myocytes to apoptosis in patients with idiopathic dilated cardiomyopathy, INT J CARD, 80(1), 2001, pp. 29-36
Citations number
32
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Background: Bcl-2 proto-oncogene, an inhibitor of apoptosis and Bax proto-o
ncogene, an inducer of apoptosis play critical roles in the molecular circu
it controlling apoptosis in cardiac muscle. The ratio of Bax to Bcl-2 proto
-oncogene determines survival or death after an apoptotic stimulus. We spec
ulated that susceptibility of myocytes to apoptosis determined as the Bax/B
cl-2 ratio might vary with the severity of heart failure. Methods and resul
ts: We studied immunohistochemically 108 endomyocardial biopsy specimens fr
om 30 patients with idiopathic dilated cardiomyopathy (mild heart failure,
n = 14; moderate or severe heart failure, n = 16) with the use of Bcl-2 and
Bax monoclonal antibodies. The expression of each protein was determined s
emiquantitatively as the fraction of myocytes labeled with specific monoclo
nal antibodies using a digital morphometric analysis system. Patients with
mild heart failure showed significantly increased Bax/Bcl-2 ratio than the
patients with advanced heart failure 1.59 +/-1.26 vs. 0.34 +/-0.43, P=0.002
). The expression of Bcl-2 was found to be independent of the severity of h
eart failure whereas the expression of Bax was significantly higher in pati
ents with mild heart failure compared to the patients with moderate or seve
re heart failure (52.1 +/- 29.3 vs. 21.6 +/- 22.4%, P=0.005). Additionally,
Bax/Bac-2 ratio was inversely correlated with the mitral E-interventricula
r septum distance, left ventricular end-systolic and end-diastolic diameter
. Conclusion: The susceptibility of myocytes to apoptosis is significantly
increased in the early phase of heart failure but it decreases with worseni
ng of the disease due to depressed expression of Bax onco-protein. Increase
d myocyte susceptibility to apoptosis may have a role in the transition fro
m mild heart failure to severe in patients with idiopathic dilated cardiomy
opathy. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.