AMPK/Sirt1-mediated inflammation is positively correlated with myocardial fibrosis during ageing

Abstract

Objectives

Cardiovascular disease is the leading cause of death in the world, and it increases dramatically with ageing. The objective of this study was to elucidate age-dependent molecular changes of inflammation and its correlation with the progression of myocardial fibrosis.

Methods

Methods: Male SD rats aged 3, 6, 9 and 24 months were used in this study. H&E staining was used to assessed histo-morphological changes in different ages. Masson’s trichrome staining was used to evaluate myocardial fibrosis. Immunofluorescence as well as western blot was carried out to detect the expression of vimentin. Real-time PCR was used to detect the level of pro-inflammatory chemokines MCP-1, IL1β, TNFα and IL-6. Western blotting was also carried out to detect p-AMPK, Sirt1, AC-NF-κB expression.

Results

Myocardial pathological changes and fibrosis are positively correlated with age. Ageing rats showed an enhanced expression of inflammatory factors and the activation of cardiac fibroblasts increases. Meanwhile, the expression of p-AMPK, Sirt1 and downstream AC-NF-κB increased significantly during ageing. Furthermore, the 15–24 months of age in rats is the fastest changing stage of increased inflammation and decreased Sirt1 activity.

Conclusions

Ageing is an independent risk factor for the occurrence and development of myocardial fibrosis. During ageing, myocardial fibroblasts are activated, accompanied by an increase in extracellular matrix deposition. The inflammation mediated by AMPK/Sirt1/NF-κB signalling pathway is closely positively correlated with the activation of myocardial fibroblasts and the progression of myocardial fibrosis.

Keywords:

• Ageing
• myocardial fibrosis
• cardiac fibroblast
• inflammation
• AMPK/Sirt1 signalling pathway
• NF-κB

Ethics statement

All experiments were carried out in accordance with the guidelines on the care and use of laboratory animals (Centre of Experimental Animals, China Three Gorges University, China). This study protocol was reviewed and approved by the ethics committee for animal experiments, China Three Gorges University, approval number 2018013 F.

Author contributions

Zhiyong Zhou and Gaigai Deng designed the project and wrote the manuscript; Yanan Song and Yaqing Zhang conducted the animal model and morphological experiments; Xulan Zhang and Shanshan Hu performed the Western blot and IF; Jin’er Wang participated in statistical analysis. All authors agreed on the final version.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data generated or analysed during this study are included in this article. Further enquiries can be directed to the corresponding author.

Additional information

Funding

This work was supported by the grant from the National Natural Science Foundation of China (NSFC) (No.81903769 to Gaigai Deng) and the Open Foundation of Yichang Key Laboratory of ischaemic cardiovascular and cerebrovascular disease translational medicine (Three Gorges University) (No. 2017KXN07 to Zhiyong Zhou).