The role of post-translational modifications in cardiac hypertrophy

Abstract

Pathological cardiac hypertrophy involves excessive protein synthesis, increased cardiac myocyte size and ultimately the development of heart failure. Thus, pathological cardiac hypertrophy is a major risk factor for many cardiovascular diseases and death in humans. Extensive research in the last decade has revealed that post-translational modifications (PTMs), including phosphorylation, ubiquitination, SUMOylation, O-GlcNAcylation, methylation and acetylation, play important roles in pathological cardiac hypertrophy pathways. These PTMs potently mediate myocardial hypertrophy responses via the interaction, stability, degradation, cellular translocation and activation of receptors, adaptors and signal transduction events. These changes occur in response to pathological hypertrophy stimuli. In this review, we summarize the roles of PTMs in regulating the development of pathological cardiac hypertrophy. Furthermore, PTMs are discussed as potential targets for treating or preventing cardiac hypertrophy.

Keywords: cardiac hypertrophy; heart failure; post-translational modifications (PTMs).

Figure 1

Ubiquitination‐mediated signalling pathways of cardiac hypertrophy. Ubiquitination plays an important role in cardiac hypertrophy by regulating the TAK1‐JNK1/2/p38, NF‐κB signalling, Ca²⁺/calmodulin, oxidation stress, ERK signalling pathways. In these pathways, pressure overload or other hypertrophic stimuli can induce E3 ligases or DUBs to activate MAPKs or other signalling pathways, ultimately regulating nuclear transcription factors to promote growth

Figure 2

SUMOylation‐mediated signalling pathway of cardiac hypertrophy. SUMOylation plays an important role in cardiac hypertrophy by regulating the Ca²⁺/calmodulin, NF‐κB and other signalling pathways

Figure 3

Acetylation‐ and methylation‐mediated signalling pathways of cardiac hypertrophy. Chromatin modifications are essential for regulating gene expression. Gene transcription can be regulated by acetylation and methylation of chromatin histones. Through remodelling the structure of chromatin, epigenetic modifications mediate the accessibility of DNA to regulate gene expression