生活方式改变和老龄化程度的加剧，使急性心肌梗死已成为影响现代人生活质量及生存率的主要疾病之一，但迄今尚缺乏有效的防治办法；从不同角度揭示调控心肌梗死的分子网络机制，对防治心肌梗死具有重要的生物和医学意义。当细胞处于缺氧等应激状态时会引发内质网应激（ERs）反应(UPR)。研究提示这种应激反应与心血管疾病发生发展密切相关，但具体机制尚不清楚。线粒体对内质网应激反应非常敏感，但心梗过程中是否存在“内质网应激-线粒体对话”及其作用尚且不知。基于前期工作基础，本项目立项研究LncRNA-Gm12840对急性心梗早期内质网应激的调控作用，探讨其是否通过促进内质网应激反应因子Grp94的表达，抑制OPA1蛋白水解为S-OPA1，减缓线粒体分裂，改善线粒体损伤和心肌活力，减缓心梗后心肌损伤。本项目研究从“内质网应激-线粒体对话”角度出发，有望通过ERs途径为研发心血管疾病新药物、新治疗方式提供新的方向。

Due to the changes in lifestyle and the aging of the elderly, acute myocardial infarction has become to the leading cause of morbidity and mortality worldwide, harming the quality of life and survival rate of modern people. However, there is still no effective prevention strategy. It has important biological and medical significance for the prevention and treatment of myocardial infarction to thoroughly reveal the molecular mechanisms network regulating the onset and development of myocardial infarction from different aspects. Endoplasmic reticulum stress (ERs) response (UPR) is triggered when cells are under stress conditions such as hypoxia. Studies suggest that ER stress response is closely related to the development of cardiovascular disease, but the detailed mechanisms are still unclear. Mitochondria are very sensitive to ER stress response, but that whether endoplasmic reticulum stress-mitochondrial crosstalk participates in myocardial infarction is unknown. Based on our preliminary work, this project aims to investigate the regulation of LncRNA-Gm12840 on early endoplasmic reticulum stress in acute myocardial infarction, and explore whether it inhibits OPA1 proteolysis to S-OPA1 through promoting endoplasmic reticulum stress response factor Grp94 expression, leading to attenuated mitochondrial damage and myocardial damage caused by myocardial infarction. Through exploring endoplasmic stress-mitochondrial crosstalk and its regulatory factors, this project is expected to provide a new direction for the development of new drugs and new treatments for cardiovascular diseases.