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pathogenesis of heart failure. A number of noxic stressors are found to cause the changes
in the Bcl levels resulting in the apoptosis of cardiac myocytes. These stressors include
oxidative stress, hypoxia and reoxygenation, stretch, chronic pressure overload and
myocardial infraction (Condorelli et al. 1999; Cook et al. 1999; Kajstura et al. 1996;
Kang et al. 2000a; Misao et al. 1996). The exposure of isolated cardiac myocytes to
oxidative stress was found to cause the incorporation of Bax and Bad into mitochondrial
membranes, heterodimerization of Bcl-2 and release of cytochrome C in to the cytosolic
compartment (Cook et al. 1999; von Harsdorf et al. 1999). The exposure of isolated
cardiac myocytes to cytokines was also found to cause the upregulation of proapoptotic
factor Bax (Ing et aI1999). Di Napoli et al. (2003) has reported that the increase in the
left ventricular wall stress in the hearts of patients suffering from severe dilated
cardiomyopathy has resulted in the increased expression of Bax in subendocardial cardiac
cells (Di Napoli et al. 2003), The increase in Bax was found to correiate with the
increased incidence of apoptosis and changes in the B,axlBcl-Z ratio (Di Napoli et al.
2003).
A recently identified member of Bcl-2 family, BCL-xl, has received a significant
attention due to its confirmed anti-apoptotic effects on the heart. Bcl-xl's anti-apoptotic
effects were confirmed in a number of studies involving a variety of ceils types
(Zamzami et al. 1998). It is also shown that the number of growth factors such as insulinlike
growth factor-l (IGF-l), bone morphogenic protein 2 and hepatocyte growth factor
(HGF) are able to increase the expression of BCI-xl (Izumi et al. 2001; Nakamura et al.
2000; Yamamura et al. 2001) . Bcl-xl expression in isolated cardiac myocytes is also
stimulated by the administration of vasoconstrictory peptide endothelin 1 (ET-1), which
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