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天冬酰胺耗竭介导高强度运动诱发的心脏损伤:来自代谢组学和孟德尔随机化的转化证据。

Asparagine depletion mediates high-intensity exercise induced cardiac injury: translational evidence from metabolomics and Mendelian randomization.

作者信息

Kang Ji, Xu Zhaohui, Duan Yuanchao, Li Tianyou

机构信息

Department of Internal Medicine, Hospital of Bojishan, Jinan, 250002, Shandong Province, People's Republic of China.

出版信息

Eur J Appl Physiol. 2025 Aug 29. doi: 10.1007/s00421-025-05957-1.

DOI:10.1007/s00421-025-05957-1
PMID:40879772
Abstract

BACKGROUND

Exercise is an important method of promoting health. But unscientific high-intensity exercise is harmful to health. Extreme high-intensity exercise could lead to serious cardiac events such as sudden cardiac death. However, myocardial injury and the metabolic changes have been little studied. Our study aimed to explore the changes in myocardial tissue and metabolism after high-intensity exercise, while investigating the relationship between key metabolites and diseases that cause myocardial injury in population.

METHODS

We investigated myocardial injury through serum myocardial injury markers and myocardial pathology in mice after single exhaustion swimming. Machine learning combined with metabolomics were used to study myocardial metabolic changes and select key metabolites. Mendelian randomization was utilized to test the applicability of the results of animal experiments in the population.

RESULTS

Our study found that high-intensity exercise resulted in significant elevation of serum markers of myocardial injury, significant pathological changes in the myocardium, and significant alterations in myocardial metabolism. Mendelian randomization revealed that decreased expression of the key metabolite asparagine might associate with chronic ischemic heart disease, consistent with the results of animal experiments.

CONCLUSIONS

This study found that high-intensity exercise could cause myocardial injury and significantly affect myocardial metabolic profiles. The selected key metabolite asparagine was a protective factor against chronic ischemic heart disease in population. Our study provides new insights into high-intensity exercise-associated myocardial injury and new strategies for human health protection.

摘要

背景

运动是促进健康的重要方法。但不科学的高强度运动对健康有害。极端高强度运动可能导致严重的心脏事件,如心源性猝死。然而,心肌损伤和代谢变化的研究较少。我们的研究旨在探讨高强度运动后心肌组织和代谢的变化,同时调查关键代谢物与人群中导致心肌损伤的疾病之间的关系。

方法

我们通过单次力竭游泳后小鼠的血清心肌损伤标志物和心肌病理学来研究心肌损伤。采用机器学习结合代谢组学来研究心肌代谢变化并筛选关键代谢物。利用孟德尔随机化来检验动物实验结果在人群中的适用性。

结果

我们的研究发现,高强度运动导致心肌损伤血清标志物显著升高、心肌出现明显病理变化以及心肌代谢显著改变。孟德尔随机化显示,关键代谢物天冬酰胺表达降低可能与慢性缺血性心脏病有关,这与动物实验结果一致。

结论

本研究发现,高强度运动可导致心肌损伤并显著影响心肌代谢谱。所筛选出的关键代谢物天冬酰胺是人群中慢性缺血性心脏病的保护因素。我们的研究为高强度运动相关心肌损伤提供了新见解以及人类健康保护的新策略。

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