Heart failure remains a common and difficult-to-treat medical condition with the average 5-year mortality about 40%, reflecting an urgent need for effective therapeutics.
A new study published in Science Translational Medicine has shown that the inhibition of the epigenetic regulator bromodomain-containing protein 4 (BRD4) using the small molecule JQ1 attenuates the progression of heart failure (HF) in mice. BRD4, a member of the bromodomain and extraterminal family of epigenetic regulators and the target of JQ1, plays a role in the development of heart failure and contributes to cardiomyocyte hypertrophy.
Saptarsi Haldar and colleagues used a combination of mouse and human induced pluripotent stem cell–derived cardiomyocyte models to show that JQ1 can reverse the detrimental effects of BRD4 and improve cardiac structure and function even in the setting of prolonged and severe disease. In addition, the investigators found that JQ1 did not interfere with physiological cardiac hypertrophy that occurs in response to exercise, supporting the safety of this approach.
The findings suggest that the inhibition of BRD4 with a small molecule alleviates HF through the modulation of specific transcriptional programmes.