HDAC and HDAC Inhibitor: From Cancer to Cardiovascular Diseases

Abstract

Histone deacetylases (HDACs) are epigenetic regulators that regulate the histone tail, chromatin conformation, protein-DNA interaction, and even transcription. HDACs are also post-transcriptional modifiers that regulate the protein acetylation implicated in several pathophysiologic states. HDAC inhibitors have been highlighted as a novel category of anti-cancer drugs. To date, four HDAC inhibitors, Vorinostat, Romidepsin, Panobinostat, and Belinostat, have been approved by the United States Food and Drug Administration. Principally, these HDAC inhibitors are used for hematologic cancers in clinic with less severe side effects. Clinical trials are continuously expanding to address other types of cancer and also nonmalignant diseases. HDAC inhibition also results in beneficial outcomes in various types of neurodegenerative diseases, inflammation disorders, and cardiovascular diseases. In this review, we will briefly discuss 1) the roles of HDACs in the acquisition of a cancer's phenotype and the general outcome of the HDAC inhibitors in cancer, 2) the functional relevance of HDACs in cardiovascular diseases and the possible therapeutic implications of HDAC inhibitors in cardiovascular disease.

Keywords: Cardiovascular diseases; Histone deacetylase inhibitors; Histone deacetylases; Neoplasms.

FIG. 1. The role of HDACs in cancer biology. Generally HDACs participate in the expression of malignant phenotypes in cancer cells. Class I HDACs promote cell proliferation and inhibit both apoptosis and differentiation. Class II HDACs provoke tumor angiogenesis. HDAC6 specifically increase in cell motility which results in distant metastasis. The bar indicates suppression whereas the arrow depicts stimulation.

FIG. 2. The therapeutic potential of HDAC inhibitors in cardiovascular disease. HDAC inhibitors have been reported to show beneficial outcomes for cardiac arrhythmia, cardiac fibrosis, cardiac hypertrophy, and myocardial infarction. Although several debates in atherosclerosis, HDAC inhibitors also significantly reduce the progression of atherosclerosis. Vascular calcification, however, may be aggravated by HDAC inhibitors. The bar indicates suppression whereas the arrow depicts stimulation. The dash arrow reflects controversial effects.