Retinoid-dependent pathways suppress myocardial cell hypertrophy.
MD Zhou, HM Sucov, RM Evans… - Proceedings of the …, 1995 - National Acad Sciences
Proceedings of the National Academy of Sciences, 1995•National Acad Sciences
Utilizing an in vitro model system of cardiac muscle cell hypertrophy, we have identified a
retinoic acid (RA)-mediated pathway that suppresses the acquisition of specific features of
the hypertrophic phenotype after exposure to the alpha-adrenergic receptor agonist
phenylephrine. RA at physiological concentrations suppresses the increase in cell size and
induction of a genetic marker for hypertrophy, the atrial natriuretic factor (ANF) gene. RA also
suppresses endothelin 1 pathways for cardiac muscle cell hypertrophy, but it does not affect …
retinoic acid (RA)-mediated pathway that suppresses the acquisition of specific features of
the hypertrophic phenotype after exposure to the alpha-adrenergic receptor agonist
phenylephrine. RA at physiological concentrations suppresses the increase in cell size and
induction of a genetic marker for hypertrophy, the atrial natriuretic factor (ANF) gene. RA also
suppresses endothelin 1 pathways for cardiac muscle cell hypertrophy, but it does not affect …
Utilizing an in vitro model system of cardiac muscle cell hypertrophy, we have identified a retinoic acid (RA)-mediated pathway that suppresses the acquisition of specific features of the hypertrophic phenotype after exposure to the alpha-adrenergic receptor agonist phenylephrine. RA at physiological concentrations suppresses the increase in cell size and induction of a genetic marker for hypertrophy, the atrial natriuretic factor (ANF) gene. RA also suppresses endothelin 1 pathways for cardiac muscle cell hypertrophy, but it does not affect the increase in cell size and ANF expression induced by serum stimulation. A trans-activation analysis using a transient transfection assay reveals that neonatal rat ventricular myocardial cells express functional RA receptors of both the retinoic acid receptor and retinoid X receptor (RAR and RXR) subtypes. Using synthetic agonists of RA, which selectively bind to RXR or RAR, our data indicate that RAR/RXR heterodimers mediate suppression of alpha-adrenergic receptor-dependent hypertrophy. These results suggest the possibility that a pathway for suppression of hypertrophy may exist in vivo, which may have potential therapeutic value.
National Acad Sciences