Bromodomain inhibition halts heart failure

Access through your institution Buy or subscribe Heart failure (HF) is the leading cause of mortality in modern society. It is a consequence of pathological remodelling of the heart, which

involves cardiac hypertrophy (a robust predictor of subsequent HF and death), fibrosis and inflammation. At the molecular level, HF has been associated with chromatin hyperacetylation. Now,

reporting in _Cell_, Anand _et al_. show that the BET family bromodomain proteins (BETs), a family of acetyl-lysine reader proteins, are central to HF pathogenesis and that they are

promising targets for the prevention of HF. The group utilized the recently developed first-in-class inhibitor JQ1, which displaces BETs from chromatin, resulting in the suppression of

downstream signalling to RNA polymerase II (Pol II). Investigating the role of BETs in an _in vitro_ model of neurohormonally induced heart disease, the authors showed that nanomolar doses

of JQ1 significantly blocked phenylephrine-mediated hypertrophy of cardiomyocytes and pathological gene induction. Similar results were achieved through knockdown of the BET

bromodomain-containing protein 4 (BRD4), which is highly expressed in cardiac tissues. Gene expression profiling of cultured cardiomyocytes in the presence or absence of JQ1 showed that the

drug abrogated the induction of a substantial subset of phenylephrine-induced genes. This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your

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Read our FAQs * Contact customer support REFERENCES * Anand, P. et al. BET bromodomains mediate transcriptional pause release in heart failure. _Cell_ 154, 569–582 (2013) Article  CAS 

Google Scholar  Download references Authors * Alexandra Flemming View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and

permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Flemming, A. Bromodomain inhibition halts heart failure. _Nat Rev Drug Discov_ 12, 741 (2013). https://doi.org/10.1038/nrd4134 Download

citation * Published: 01 October 2013 * Issue Date: October 2013 * DOI: https://doi.org/10.1038/nrd4134 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this

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