Estrogen regulates histone deacetylases to prevent cardiac hypertrophy

Ali Pedrama, Mahnaz Razandi, Ramesh Narayanan, James T. Dalton, Timothy A. McKinsey, Ellis R. Levin

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

The development and progression of cardiac hypertrophy often leads to heart failure and death, and important modulators of hypertrophy include the histone deacetylase proteins (HDACs). Estrogen inhibits cardiac hypertrophy and progression in animal models and humans. We therefore investigated the influence of 17-β-estradiol on the production, localization, and functions of prohypertrophic (class I) and antihypertrophic (class II) HDACs in cultured neonatal rat cardiomyocytes. 17-β-Estradiol or estrogen receptor β agonists dipropylnitrile and β-LGND2 comparably suppressed angiotensin II-induced HDAC2 (class I) production, HDAC-Activating phosphorylation, and the resulting prohypertrophic mRNA expression. In contrast, estrogenic compounds derepressed the opposite effects of angiotensin II on the same parameters for HDAC4 and 5 (class II), resulting in retention of these deacetylases in the nucleus to inhibit hypertrophic gene expression. Key aspects were confirmed in vivo from the hearts of wild-type but not estrogen receptor β (ERβ) gene-deleted mice administered angiotensin II and estrogenic compounds. Our results identify a novel dual regulation of cardiomyocyte HDACs, shown here for the antihypertrophic sex steroid acting at ERβ. This mechanism potentially supports using ERβ agonists as HDAC modulators to treat cardiac disease.

Original languageEnglish (US)
Pages (from-to)3805-3818
Number of pages14
JournalMolecular Biology of the Cell
Volume24
Issue number24
DOIs
StatePublished - Dec 15 2013

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Histone Deacetylases
Cardiomegaly
Estrogens
Angiotensin II
Cardiac Myocytes
Estrogen Receptors
Estradiol Receptors
Hypertrophy
Estradiol
Heart Diseases
Animal Models
Heart Failure
Steroids
Phosphorylation
Gene Expression
Messenger RNA
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Pedrama, A., Razandi, M., Narayanan, R., Dalton, J. T., McKinsey, T. A., & Levin, E. R. (2013). Estrogen regulates histone deacetylases to prevent cardiac hypertrophy. Molecular Biology of the Cell, 24(24), 3805-3818. https://doi.org/10.1091/mbc.E13-08-0444

Estrogen regulates histone deacetylases to prevent cardiac hypertrophy. / Pedrama, Ali; Razandi, Mahnaz; Narayanan, Ramesh; Dalton, James T.; McKinsey, Timothy A.; Levin, Ellis R.

In: Molecular Biology of the Cell, Vol. 24, No. 24, 15.12.2013, p. 3805-3818.

Research output: Contribution to journalArticle

Pedrama, A, Razandi, M, Narayanan, R, Dalton, JT, McKinsey, TA & Levin, ER 2013, 'Estrogen regulates histone deacetylases to prevent cardiac hypertrophy', Molecular Biology of the Cell, vol. 24, no. 24, pp. 3805-3818. https://doi.org/10.1091/mbc.E13-08-0444
Pedrama, Ali ; Razandi, Mahnaz ; Narayanan, Ramesh ; Dalton, James T. ; McKinsey, Timothy A. ; Levin, Ellis R. / Estrogen regulates histone deacetylases to prevent cardiac hypertrophy. In: Molecular Biology of the Cell. 2013 ; Vol. 24, No. 24. pp. 3805-3818.
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