il\VOLVEMENT OF RETII\OIC ACID II{ - MSpace at the University of ...

Treatment with adriamycin has been shown to cause oxidative stress (Doroshow
1983; Rajagopalan et al. 1988; Singal and Iliskovic 1998) and adriamycin-induced
oxidative stress is a major factor involved in the pathogenesis oî adriamycin-induced
heart failgre (Singal and lliskovic 1998). The treatment with adriamycin, in other studies,
was also found to result in an increase in apoptosis in vivo as well as in vitro (Kumar et
al. 1999;Kumar et al. 2001). Since apoptosis has been suggested to be involved in the
pathogenesis of heart failure (Sharov et al. 1996; Thompson 1995), it is likely that
oxidative stress mediated apoptosis may be an important factor in the pathogenesis of
adriamycin-induced heart failure.
IV. RARIRXR receptor ratio and its significance
Role of retinoic acid in heart physiology has been examined to a great extent
during the embryonic development, while its role in the adult cardiovascular system is
still unknown. It is known fhat anumber of cardiovascular diseases and heart failure are
charactenzed by the activation of embryonic genes and embryonic phenotype (Parker
1995). The development of heart failure is also found to be accompanied by the
occuïïence of cardiomyocyte apoptosis and changes in the ventricular wall thickness and
architecture (Foo et al. 2005). Since retinoic acid is involved in embryogenesis,
apoptosis, celI proliferation and cell differentiation and since these effects are regulated
through the activation of retinoic acid receptors, the present study has followed the
expression of retinoic acid receptors during the pathogenesis of congestive heart failure
due to adriamycin.
We undertook a detailed study of different isoforms of RAR and RXR receptors
which included: RAR cr, RAR p, RAR y; and RXR ü, RXR p, RXR y. Furthermore, we
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