Therapeutic effects of histone deacetylase inhibitors on heart disease.

A wide range of histone deacetylase (HDAC) inhibitors have been studied for their therapeutic potential because the excessive activity and expression of HDACs have been implicated in the pathogenesis of cardiac diseases. An increasing number of preclinical studies have demonstrated the cardioprotective effects of numerous HDAC inhibitors, suggesting a wide variety of mechanisms by which the inhibitors protect against cardiac stress, such as the suppression of cardiac fibrosis and fetal gene expression, enhancement of angiogenesis and mitochondrial biogenesis, prevention of electrical remodeling, and regulation of apoptosis, autophagy, and cell cycle arrest. For the development of isoform-selective HDAC inhibitors with high efficacy and low toxicity, it is important to identify and understand the mechanisms responsible for the effects of the inhibitors. This review highlights the preclinical effects of HDAC inhibitors that act against Zn2+-dependent HDACs and the underlying mechanisms of their protective effects against cardiac hypertrophy, hypertension, myocardial infarction, heart failure, and atrial fibrillation.