@article{eadd4266f111456d9107273a95523ae8,
title = "Titrating autophagy in cardiac plasticity",
abstract = "The heart is a highly plastic organ. In a recent study, we found that autophagy is a required element in load-induced cardiomyocyte growth; when autophagy is suppressed, the heart does not grow. Conversely, afterload stress triggers a transient increase in cardiomyocyte autophagic activity which settles to a new-higher-baseline once the heart has re-achieved steady-state size. Our work went on to decipher the role of histone deacetylases in this biology.",
keywords = "Heart, Heart failure, Histone deacetylase, Hypertrophy, Remodeling",
author = "Cao, {Dian J} and Hill, {Joseph A}",
note = "Funding Information: Next, we capitalized on our prior transgenic mice to surgical constriction of In aggregate, this study uncovers car-observation that amplification of stress-the thoracic aorta, thereby eliciting ven-diomyocyte autophagy as a required ele-induced autophagy by cardiomyocyte-tricular growth, dilatation and systolic ment of pathological cardiac growth. specific overexpression of Beclin 1 leads to dysfunction. Only after all three of these Second, it points to the functional require-a dramatically amplified growth response, were observed did we initiate drug ther-ment of HDACs, specifically HDAC1 and accelerated fibrogenesis and robust ventric-apy. Remarkably, we observed that small HDAC2, in this response. Third, it raises ular dilatation and declines in contractile molecule HDAC inhibition in these ani-the prospect of targeting cardiomyocyte performance. From this prior observation, mals with robust heart disease is capable autophagy therapeutically using small we inferred that Beclin 1-dependent proof returning systolic function completely molecule inhibitors of HDACs. cesses, including activation of autophagy, back to normal, and regresses ventricular are capable of promoting pathological mass significantly. cardiac remodeling. Given this, we asked As autophagy is critical to protein We thank members of the Hill lab for valu-whether HDAC inhibition could blunt and organelle quality control, beneficial able suggestions and comments. This work pathological cardiac growth even when it effects from its inhibition are at one level was supported by grants from the NIH is amplified by “dialing up” the autophagic counterintuitive. However, emerging evi-(HL-075173; HL-080144; HL-090842), response. In fact, we found that small dence points to a requirement that auto-AHA (0640084N), ADA (7-08-MN-21-molecule inhibitors of HDACs are able phagic activation remain fixed within a ADA) and the AHA-Jon Holden DeHaan to reset the load-induced growth response zone where its adaptive effects can take Foundation (0970518N).",
year = "2011",
month = sep,
doi = "10.4161/auto.7.9.16176",
language = "English (US)",
volume = "7",
pages = "1078--1079",
journal = "Autophagy",
issn = "1554-8627",
publisher = "Landes Bioscience",
number = "9",
}