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MG53 Protects against Sepsis-Induced Myocardial Dysfunction by Upregulating Peroxisome Proliferator-Activated
Xue Han1, Daili Chen2, Ning Liufu1
1Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
Background:
The heart is one of the most commonly affected organs during sepsis. Mitsugumin-53 (MG53) has attracted attention in research due to its cardioprotective function. However, the role of MG53 in sepsis-induced myocardial dysfunction (SIMD) remains unknown. The purpose of this study was to explore the underlying mechanism of MG53 in SIMD and investigate its potential relationship with peroxisome proliferator-activated receptor-α (PPARα).
Methods:
The cecal ligation and puncture (CLP) model was created to induce SIMD in rats. Protein levels of MG53 and PPARα, cardiac function, cardiomyocyte injury, myocardial oxidative stress and inflammatory indicators, and cardiomyocyte apoptosis were measured at 18 h after CLP. The effects of MG53 on PPARα in SIMD were investigated via preconditioning recombinant human MG53 (rhMG53) and PPARα antagonist GW6471.
Results:
The expression of MG53 and PPARα sharply decreased in the myocardium at 18 h after CLP. Compared with the sham group, cardiac function was significantly depressed, which was associated with the destructed myocardium, upregulated oxidative stress indicators and proinflammatory cytokines, and excessive cardiomyocyte apoptosis in the CLP group. Supplementation with rhMG53 enhanced myocardial MG53, increased the survival rate with improved cardiac function, and reduced oxidative stress, inflammation, and myocardial apoptosis, which were associated with PPARα upregulation. Pretreatment with GW6471 abolished the abovementioned protective effects induced by MG53.
Conclusions:
Both MG53 and PPARα were downregulated after sepsis shock. MG53 supplement protects the heart against SIMD by upregulating PPARα expression. Our results provide a new treatment strategy for SIMD.
Insights
Mitsugumin-53 (MG53) protects the heart during sepsis by increasing peroxisome proliferator-activated receptor-alpha (PPARα). This study reveals MG53
Area of Science:
- Biomedical research
- Cardiovascular science
- Sepsis research
Background:
- Sepsis commonly affects the heart, leading to sepsis-induced myocardial dysfunction (SIMD).
- Mitsugumin-53 (MG53) exhibits cardioprotective properties, but its role in SIMD is unclear.
- Peroxisome proliferator-activated receptor-alpha (PPARα) is a potential regulator in cardiac function.
Purpose of the Study:
- To elucidate the mechanism of MG53 in SIMD.
- To investigate the relationship between MG53 and PPARα in the context of sepsis-induced heart dysfunction.
Main Methods:
- A cecal ligation and puncture (CLP) model was used to induce SIMD in rats.
- MG53 and PPARα levels, cardiac function, and myocardial injury markers were assessed post-CLP.
- The impact of recombinant human MG53 (rhMG53) and a PPARα antagonist (GW6471) on SIMD was evaluated.
Main Results:
- CLP induced decreased myocardial expression of MG53 and PPARα, alongside impaired cardiac function, increased oxidative stress, inflammation, and cardiomyocyte apoptosis.
- rhMG53 administration improved cardiac function, survival rates, and reduced myocardial damage, correlating with PPARα upregulation.
- Inhibition of PPARα by GW6471 negated the protective effects of MG53.
Conclusions:
- Both MG53 and PPARα are downregulated in sepsis-induced myocardial dysfunction.
- MG53 supplementation offers cardioprotection in SIMD by upregulating PPARα.
- These findings suggest a novel therapeutic strategy targeting MG53 and PPARα for SIMD treatment.
