Insights into the post-translational modifications in heart failure

Abstract

Heart failure (HF), as the terminal manifestation of multiple cardiovascular diseases, causes a huge socioeconomic burden worldwide. Despite the advances in drugs and medical-assisted devices, the prognosis of HF remains poor. HF is well-accepted as a myriad of subcellular dys-synchrony related to detrimental structural and functional remodelling of cardiac components, including cardiomyocytes, fibroblasts, endothelial cells and macrophages. Through the covalent chemical process, post-translational modifications (PTMs) can coordinate protein functions, such as re-localizing cellular proteins, marking proteins for degradation, inducing interactions with other proteins and tuning enzyme activities, to participate in the progress of HF. Phosphorylation, acetylation, and ubiquitination predominate in the currently reported PTMs. In addition, advanced HF is commonly accompanied by metabolic remodelling including enhanced glycolysis. Thus, glycosylation induced by disturbed energy supply is also important. In this review, firstly, we addressed the main types of HF. Then, considering that PTMs are associated with subcellular locations, we summarized the leading regulation mechanisms in organelles of distinctive cell types of different types of HF, respectively. Subsequently, we outlined the aforementioned four PTMs of key proteins and signaling sites in HF. Finally, we discussed the perspectives of PTMs for potential therapeutic targets in HF.