The role of histone deacetylases in cardiac energy metabolism in heart diseases

Metabolism. 2023 May:142:155532. doi: 10.1016/j.metabol.2023.155532. Epub 2023 Mar 6.

Abstract

Heart diseases are associated with substantial morbidity and mortality worldwide. The underlying mechanisms and pathological changes associated with cardiac diseases are exceptionally complex. Highly active cardiomyocytes require sufficient energy metabolism to maintain their function. Under physiological conditions, the choice of fuel is a delicate process that depends on the whole body and organs to support the normal function of heart tissues. However, disordered cardiac metabolism has been discovered to play a key role in many forms of heart diseases, including ischemic heart disease, cardiac hypertrophy, heart failure, and cardiac injury induced by diabetes or sepsis. Regulation of cardiac metabolism has recently emerged as a novel approach to treat heart diseases. However, little is known about cardiac energy metabolic regulators. Histone deacetylases (HDACs), a class of epigenetic regulatory enzymes, are involved in the pathogenesis of heart diseases, as reported in previous studies. Notably, the effects of HDACs on cardiac energy metabolism are gradually being explored. Our knowledge in this respect would facilitate the development of novel therapeutic strategies for heart diseases. The present review is based on the synthesis of our current knowledge concerning the role of HDAC regulation in cardiac energy metabolism in heart diseases. In addition, the role of HDACs in different models is discussed through the examples of myocardial ischemia, ischemia/reperfusion, cardiac hypertrophy, heart failure, diabetic cardiomyopathy, and diabetes- or sepsis-induced cardiac injury. Finally, we discuss the application of HDAC inhibitors in heart diseases and further prospects, thus providing insights into new treatment possibilities for different heart diseases.

Keywords: Cardiac energy metabolism; Cardiac hypertrophy; Diabetic cardiomyopathy; Heart failure; Histone deacetylases; Myocardial ischemia/reperfusion.

Publication types

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

MeSH terms

  • Cardiomegaly
  • Diabetes Mellitus* / metabolism
  • Energy Metabolism
  • Heart Diseases* / drug therapy
  • Heart Diseases* / etiology
  • Heart Diseases* / metabolism
  • Heart Failure* / drug therapy
  • Histone Deacetylases
  • Humans
  • Myocytes, Cardiac / metabolism

Substances

  • Histone Deacetylases