Multi-omics analysis of early reperfused ischemic heart reveals ERRβ/γ activation protects against acute myocardial infarction injury

作者：Yun Gao, Fei Huang, Yuan Zhang, Dongwu Lai, Jiuxiao Zhao, Yuwen Lu, Liyin Shen, Liyin Shen, Fanwei Ruan, Zhe Zhang, Jin He, Yan Liu, Ling Tao, Guosheng Fu, Yang Zhu, Li Shen, Li Shen, Lenan Zhuang · 发表于：Journal of Advanced Research · 年份：2025 · DOI：10.1016/j.jare.2025.12.021 · 被引用次数：1 · 研究领域：Cardiac Fibrosis and Remodeling、Cardiac electrophysiology and arrhythmias、Endoplasmic Reticulum Stress and Disease

• Multi-Omics Analysis: We provide novel insights into the transcriptional and metabolic reprogramming triggered by ETR as compared with LTR, highlighting the roles of cardiomyocyte energenesis and dedifferentiation. • Cardiomyocyte Diversity: Single-nucleus RNA sequencing revealed distinct cardiomyocyte subpopulations preserved by ETR relative to LTR, offering new insights into heart repair mechanisms. • ERRβ/γ Activation: We demonstrate the therapeutic potential of ERRβ/γ activation in enhancing ETR protection, suggesting a promising strategy for AMI treatment. Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality globally, with timely percutaneous coronary intervention (PCI) as the standard treatment. Early time reperfusion (ETR) shown to reduce arrhythmias and improved survival rates compared to late time reperfusion (LTR). However, cellular and molecular mechanisms underlying the protective effects of ETR effects relative to LTR on AMI remain poorly understood. This study aims to elucidate these mechanisms through an integrated multi-omics approach, focusing on cardiomyocyte energenesis and dedifferentiation, while also exploring the therapeutic potential of ERRβ/γ activation. AMI was induced in rats by ligating the left anterior descending coronary artery (LAD) for one hour (ETR) or six hours (LTR), followed by reperfusion. Sham-operated rats served as controls. Comprehensive analyses of the ischemic hearts were performed using bulk tissue tran...