The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Histone deacetylase (HDAC) inhibitors attenuate cardiac hypertrophy by suppressing autophagy
Open accessAbstract
Histone deacetylases (HDACs) regulate cardiac plasticity; however, their molecular targets are unknown. As autophagy contributes to pathological cardiac remodeling, we hypothesized that HDAC inhibitors target autophagy. The prototypical HDAC inhibitor (HDACi), trichostatin A (TSA), attenuated both load- and agonist-induced hypertrophic growth and abolished the associated activation of autophagy. Phenylephrine (PE)-triggered hypertrophy and autophagy in cultured cardiomyocytes were each blocked by a panel of structurally distinct HDAC inhibitors. RNAi-mediated knockdown of either Atg5 or Beclin 1, two essential autophagy effectors, was similarly capable of suppressing ligand-induced autophagy and myocyte growth. RNAi experiments uncovered the class I isoforms HDAC1 and HDAC2 as required for the autophagic response. To test the functional requirement of autophagic activation, we studied mice that overexpress Beclin 1 in cardiomyocytes. In these animals with a fourfold amplified autophagic response to TAC, TSA abolished TAC-induced increases in autophagy and blunted load-induced hypertrophy. Finally, we subjected animals with preexisting hypertrophy to HDACi, finding that ventricular mass reverted to near-normal levels and ventricular function normalized completely. Together, these data implicate autophagy as an obligatory element in pathological cardiac remodeling and point to HDAC1/2 as required effectors. Also, these data reveal autophagy as a previously unknown target of HDAC inhibitor therapy.
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Cites
Heart Disease and Stroke Statistics—2012 Update: A Report From the American Heart Association
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HDAC2 negatively regulates memory formation and synaptic plasticity
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Unraveling the hidden catalytic activity of vertebrate class IIa histone deacetylases
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Cardiac hypertrophy is not a required compensatory response to short-term pressure overload
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Cited by
Histone Deacetylase Inhibitors as Anticancer Drugs
Eckschlager, T., Plch, J., Stiborova, M., & Hrabeta, J. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18071414 · Cited by 1,206
The miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy
Ucar, A., Gupta, S. K., Fiedler, J., Erikci, E., Kardasinski, M., Batkai, S., Dangwal, S., Kumarswamy, R., Bang, C., Holzmann, A., et al. (2012) · Nature Communications · doi:10.1038/ncomms2090 · Cited by 610
The Role of Autophagy in the Heart
Sciarretta, S., Maejima, Y., Zablocki, D., & Sadoshima, J. (2018) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021317-121427 · Cited by 547
Autophagy in cardiovascular biology
Lavandero, S., Chiong, M., Rothermel, B. A., & Hill, J. A. (2015) · Journal of Clinical Investigation · doi:10.1172/jci73943 · Cited by 331
Self-citationModulation of Autophagy by BDNF Underlies Synaptic Plasticity
Nikoletopoulou, V., Sidiropoulou, K., Kallergi, E., Dalezios, Y., & Tavernarakis, N. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.06.005 · Cited by 280
Metadata
- Authors
- Cao, D. J., Wang, Z. V., Battiprolu, P. K., Jiang, N., Morales, C. R., Kong, Y., Rothermel, B. A., Gillette, T. G., & Hill, J. A.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2011-02-18
- Volume
- 108
- Issue
- 10
- Pages
- 4123-4128
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2131438908
- Cited by
- 405
- References
- 11
- FWCI
- 23.99
- Type
- journal article
- Language
- en
- Open access
- green
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- Cao, D. J., Wang, Z. V., Battiprolu, P. K., Jiang, N., Morales, C. R., Kong, Y., Rothermel, B. A., Gillette, T. G., & Hill, J. A. (2011). Histone deacetylase (HDAC) inhibitors attenuate cardiac hypertrophy by suppressing autophagy. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1015081108
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