Targeting HDAC6 and its novel E3 ligase activity: A dual-strategy for cardiovascular therapy

Cardiovascular disease, the leading cause of death worldwide, imposing an enormous economic burden on society. Histone deacetylase 6 (HDAC6), a member of the class IIb HDAC family, contains two tandem deacetylase domains. Recent study reported that the first deacetylase domain of HDAC6 exerts E3 ligase activity. It is known that HDAC6 participates in a variety of cellular activities including microtubule stability, epithelial homeostasis and autophagy by modulating its specific non-histone substrates. However, the role of HDAC6 and its selective inhibitors in cardiovascular disease remains unclear. In this paper, we focus on the role of HDAC6 in the heart, as well as in the progression of cardiovascular disease including heart failure, cardiomyopathy, cardiotoxicity and myocardial infarction. We find that the expression of HDAC6 is elevated in various cardiovascular diseases, suggesting that HDAC6 may act as a biomarker for cardiovascular disease. We further discuss the potential of depletion of Hdac6 or the application of its selective inhibitors in disease prevention and treatment. Elucidation of these issues indicate that HDAC6 and its selective inhibitors might act as potential therapeutic targets for cardiovascular disease.