Jie Xiang,1,2,* Shijie Shao,1,2,* Jie Huang,3 Na Yang,1,2 Fei Guo,4 Baopeng Tang,1,2 Ling Zhang1,2 

1Xinjiang Key Laboratory of Cardiac Electrophysiology and Remodeling, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 2Department of Pacing and Electrophysiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 3Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 4Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Ling Zhang, Department of Pacing and Electrophysiology, The First Affiliated Hospital of Xinjiang Medical University, 137 Liyushan Road, Urumqi, Xinjiang, 830000, People’s Republic of China, Email ydzhangling@126.com Baopeng Tang, Department of Pacing and Electrophysiology, The First Affiliated Hospital of Xinjiang Medical University, 137 Liyushan Road, Urumqi, Xinjiang, 830000, People’s Republic of China, Email tangbaopeng1111@163.com

Background: The annual rise of global temperature and the continuous occurrence of extremely high temperatures in summer have significantly increased the incidence of heat stroke (HS), which has caused serious burden on the cardiovascular system. The purpose of this study was to investigate the potential mechanisms of heat stroke-induced myocardial injury via transcriptome sequencing.
Methods: HS models of rat and H9C2 cells were constructed and transcriptomic sequencing was performed. Bioinformatics methods were used to analyze transcriptomics to reveal the pathophysiological mechanism of HS-induced myocardial injury. Subsequently, machine learning was utilized to identify key targets of HS-induced myocardial injury. Finally, experiments such as Western blotting, flow cytometry and immunofluorescence were used to validate in vivo and in vitro.
Results: HS rats exhibited severe cardiac dysfunction. Transcriptomics revealed that HS-induced myocardial injury mainly involved apoptosis and inflammation. Meanwhile, there were significant differences in the expression of mitochondria-related genes, which were significantly enriched in the apoptosis pathway. Through machine learning, Jun was identified as a key target for HS-induced myocardial injury. In HS rat myocardial tissue, mitochondrial structure was severely disrupted, and Jun protein expression and cardiomyocyte apoptosis were significantly increased. In cell experiments, inhibition of Jun expression with Jun inhibitors (SR11302) significantly improved mitochondrial membrane potential and reduced cell apoptosis.
Conclusion: Our findings suggested that Jun-mediated mitochondrial apoptosis plays an important role in HS-induced myocardial injury, which provides a new preventive and therapeutic target for HS-induced myocardial injury.

Keywords: heat stroke, myocardial injury, apoptosis, jun, transcriptomics