Insights into the post-translational modifications in heart failure
Xudong Zhang1, Yan Wang1, Huaping Li1
1Division of Cardiology, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, 1095# Jiefang Ave, Wuhan 430030, China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China.
Insights
Post-translational modifications (PTMs) like phosphorylation and acetylation play a key role in heart failure (HF) progression. Understanding these PTMs in different cardiac cells offers new therapeutic targets for HF.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Biochemistry
Background:
- Heart failure (HF) is a major global health issue with a poor prognosis despite medical advances.
- HF involves complex subcellular dyssynchrony and detrimental remodeling of cardiac cells.
- Post-translational modifications (PTMs) are crucial regulators of protein function in cellular processes.
Purpose of the Study:
- To review the role of PTMs in the pathogenesis of different types of heart failure.
- To explore PTMs within specific subcellular locations and cell types relevant to HF.
- To identify potential therapeutic targets for HF based on PTM regulation.
Main Methods:
- Literature review focusing on PTMs in heart failure.
- Analysis of PTMs (phosphorylation, acetylation, ubiquitination, glycosylation) in distinct cardiac cell types and organelles.
- Examination of key proteins and signaling pathways affected by PTMs in HF.
Main Results:
- PTMs are integral to the detrimental remodeling observed in heart failure.
- Specific PTMs like phosphorylation, acetylation, ubiquitination, and glycosylation are implicated in HF progression.
- PTMs regulate key proteins and signaling sites within cardiomyocytes, fibroblasts, endothelial cells, and macrophages.
Conclusions:
- PTMs are critical regulators of cardiac function and dysfunction in heart failure.
- Targeting PTMs presents a promising avenue for novel therapeutic strategies in HF treatment.
- Further research into PTMs in specific HF contexts can lead to personalized treatment approaches.
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.
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