FOXOs in the impaired heart: New therapeutic targets for cardiac diseases

Biochim Biophys Acta Mol Basis Dis. 2017 Feb;1863(2):486-498. doi: 10.1016/j.bbadis.2016.11.023. Epub 2016 Nov 24.

Abstract

Cardiac diseases have a high morbidity and mortality and affect the global population. Based on recent accumulating evidence, Forkhead box O (FOXOs) play important roles in cardiac diseases. Therefore, a summary of the current literature on the molecular mechanisms and roles of FOXOs in the heart will provide valuable information. In this review, we first briefly introduce the molecular features of FOXOs. Then, we discuss the regulation and cardiac actions of the FOXO pathways. Based on this background, we expand our discussion to the roles of FOXOs in several major cardiac diseases, such as ischemic cardiac diseases, diabetic cardiomyopathy and myocardial hypertrophy. Then, we describe some methodological problems associated with the FOXO gene-modified animal models. Finally, we discuss potential future directions. The information reviewed here may be significant for the design of future studies and may increase the potential of FOXOs as therapeutic targets.

Keywords: Cardiac regeneration; Diabetic cardiomyopathy; Forkhead box O; Ischemic cardiac diseases; Myocardial hypertrophy.

Publication types

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

MeSH terms

  • Animals
  • Forkhead Box Protein O1 / analysis
  • Forkhead Box Protein O1 / genetics
  • Forkhead Box Protein O1 / metabolism*
  • Forkhead Box Protein O3 / analysis
  • Forkhead Box Protein O3 / genetics
  • Forkhead Box Protein O3 / metabolism*
  • Gene Expression Regulation
  • Heart Diseases / genetics
  • Heart Diseases / metabolism*
  • Heart Diseases / pathology
  • Humans
  • Myocardium / metabolism
  • Myocardium / pathology
  • Protein Processing, Post-Translational
  • Signal Transduction
  • Transcriptional Activation

Substances

  • Forkhead Box Protein O1
  • Forkhead Box Protein O3