Molecular switches under TGFβ signalling during progression from cardiac hypertrophy to heart failure

Br J Pharmacol. 2016 Jan;173(1):3-14. doi: 10.1111/bph.13344. Epub 2015 Nov 16.

Abstract

Cardiac hypertrophy is a mechanism to compensate for increased cardiac work load, that is, after myocardial infarction or upon pressure overload. However, in the long run cardiac hypertrophy is a prevailing risk factor for the development of heart failure. During pathological remodelling processes leading to heart failure, decompensated hypertrophy, death of cardiomyocytes by apoptosis or necroptosis and fibrosis as well as a progressive dysfunction of cardiomyocytes are apparent. Interestingly, the induction of hypertrophy, cell death or fibrosis is mediated by similar signalling pathways. Therefore, tiny changes in the signalling cascade are able to switch physiological cardiac remodelling to the development of heart failure. In the present review, we will describe examples of these molecular switches that change compensated hypertrophy to the development of heart failure and will focus on the importance of the signalling cascades of the TGFβ superfamily in this process. In this context, potential therapeutic targets for pharmacological interventions that could attenuate the progression of heart failure will be discussed.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Cardiomegaly / metabolism*
  • Cardiomegaly / pathology
  • Disease Progression
  • Energy Metabolism
  • Fibrosis / metabolism
  • Fibrosis / pathology
  • Heart Failure / metabolism*
  • Heart Failure / pathology
  • Humans
  • MAP Kinase Kinase Kinases / metabolism
  • MicroRNAs / metabolism
  • Mitochondria / metabolism
  • Models, Biological
  • Myocytes, Cardiac / pathology
  • Receptors, Adrenergic, beta / metabolism
  • Signal Transduction*
  • Transforming Growth Factor beta / metabolism*
  • Ubiquitin / metabolism
  • Ventricular Remodeling*

Substances

  • MicroRNAs
  • Receptors, Adrenergic, beta
  • Transforming Growth Factor beta
  • Ubiquitin
  • MAP Kinase Kinase Kinases
  • MAP kinase kinase kinase 7