Histone deacetylases in cardiac fibrosis: current perspectives for therapy

Cell Signal. 2014 Mar;26(3):521-7. doi: 10.1016/j.cellsig.2013.11.037. Epub 2013 Dec 7.

Abstract

Cardiac fibrosis is an important pathological feature of cardiac remodeling in heart diseases. The molecular mechanisms of cardiac fibrosis are unknown. Histone deacetylases (HDACs) are enzymes that balance the acetylation activities of histone acetyltransferases on chromatin remodeling and play essential roles in regulating gene transcription. In recent years, the role of HDACs in cardiac fibrosis initiation and progression, as well as the therapeutic effects of HDAC inhibitors, has been well studied. Moreover, numerous studies indicated that HDAC activity is associated with the development and progression of cardiac fibrosis. In this review, the innovative aspects of HDACs are discussed, with respect to biogenesis, their role in cardiac fibrosis. Furthermore, the potential applications of HDAC inhibitors in the treatment of cardiac fibrosis associated with fibroblast activation and proliferation.

Keywords: Cardiac fibrosis; ECM; Epigenetic; Extracellular matrix; FGF; Fibroblast; Fibroblast growth factor; HATs; HDACs; Histone acetyltransferases; Histone deacetylase; Histone deacetylases; Histone deacetylation; IGF-II/mannose 6-phosphate receptor; IGF-IIR/Man-6-P; MEF2; Myocyte enhancer factor-2; NRVMs; Neonatal rat ventricular myocytes; PDGF; PKD1; Platelet-derived growth factor; Proliferation; Protein kinase D1; TGF-β1; TIMPs; Tissue inhibitors of matrix metalloproteinases; Transforming growth factor β1; α-SMA; α-smooth muscle actin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetylation
  • Animals
  • Atrial Remodeling / drug effects
  • Atrial Remodeling / genetics
  • Chromatin Assembly and Disassembly / genetics
  • Fibrosis / drug therapy*
  • Fibrosis / pathology
  • Heart Diseases / drug therapy*
  • Heart Diseases / pathology
  • Histone Acetyltransferases / metabolism
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylases / classification
  • Histone Deacetylases / genetics*
  • Humans
  • Mice
  • Transcription, Genetic / genetics
  • Ventricular Remodeling / drug effects
  • Ventricular Remodeling / genetics

Substances

  • Histone Deacetylase Inhibitors
  • Histone Acetyltransferases
  • Histone Deacetylases