Exercise-induced hypertrophic preconditioning alleviates myocardial ischemic injury through trained immunity of macrophages

作者：Jichen Liu, Zhihong Li, Xinnan Wei, Dongxiao Xie, Qi Chen, Kaitong Chen, Cankun Zheng, Mingjue Li, Mingyuan He, Mengjia Shen, Lu Chen, Chi-Yu Liu, Wangjun Liao, Jianping Bin, Ziyun Guan, Qiancheng Wang, Yulin Liao, Hairuo Lin · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-025-07359-5 · 被引用次数：3 · 研究领域：Immune responses and vaccinations、Immune cells in cancer、Tryptophan and brain disorders

BACKGROUND: Physical exercise is known to induce trained immunity and improve function of macrophages, and we recently reported that exercise-induced hypertrophic preconditioning (EHP) could protect pathological hypertrophic heart, but it remains unclear whether EHP can mitigate myocardial ischemic injury. Here we hypothesized that EHP would alleviate acute myocardial ischemic injury through trained immunity of macrophages. METHODS: Swimming or treadmill running training was used to induce EHP in C57 mice. After 1-week of exercise termination, mice were subjected to myocardial ischemia/reperfusion (IR). IR injury and inflammatory response and cell energy metabolism reprogramming of bone marrow-derived macrophages (BMDMs) were analysed. Moreover, the effects of exercise on myocardial ischemic injury or long-term survival in patients with acute myocardial infarction (AMI) or history of MI were retrospectively analysed. RESULTS: EHP mice had a significantly smaller infarct size and less apoptotic cardiomyocytes than IR mice without EHP. At 4 weeks after IR, EHP mice had better cardiac function and less myocardial fibrosis. We noted less infiltration and polarization of myocardial M1 macrophages, higher expression of M2 signature anti-inflammatory factors in BMDMs of EHP mice. EHP promoted tricarboxylic acid cycle, mitochondrial oxidative phosphorylation (OXPHOS) and adenosine 5’-monophosphate activated protein kinase (AMPK) phosphorylation, decreased glycolysis and phosphorylati...