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

(Bavik et al. 1997). One of the most common features in vitamin A deficient fetuses is
the presence of spongy myocardium and intraventricular septum defects (Mahmood et al'
1992;W1LSON and Warakany J 1947). A similar pattern of deformations is found in the
RAR crl y and RXR y knockout fetuses (Kastner et al. 1994; Mendelsohn et al. 1994)'
IV.d.3.Post-natal development: In the post developmental period, retinoic acid is found
to play a significant role in the control of hypertrophy in neonatal cardiac myocytes
(Gardner and Chen lggg). Zhot et al. (1995) has reported that the administration of
retinoic acid suppressed the increase in cell size and changes in gene expression (askeletal
actin, B-myosin heavy chain and atrial natriuretic peptide), which are
characteristic of the hypertrophic response in myocyte cell cultures. This was attributed
to the activation of RAR receptors (Zhot et al. 1995). However, another study performed
by'Wu et al. (1996) indicated that hypertrophic response in neonatal cardiac myocytes to
endothelin stimulation may be attenuated by the activation of RXR receptors (Wu et al.
1996). Studies using transgene animal models (transgenic mice) have shown that the
cardiac compartment specific over expression of RXR will lead in to development of
dilated cardiomyopathy and congestive heart failure (Colbert eI al. l99l; Subbarayan et
a1. 2000). Administration of retinoic acid was found to inhibit the angiotensin ll-induced
hypertrophy and remodeling in neonatal cardiac myocytes. Wang et al' (2002) has
reported that retinoic acid treatment, in a dose dependent manner, was able to prevent the
angiotensin Il-induced hyperplasia of fibroblasts. Retinoic acid treatment was also found
to prevent the increase in the cardiac myocyte contractile protein content, increase in the
Golgi complex proteins and increase in the Ca2* content without affecting the angiotensin
II induced reorganization of sarcomeric units (Wang et al. 2002a). Retinoic acid
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