Zhou Lu, Zhu Xizi, Lei Shaoqing, Wang Yafeng, Xia Zhongyuan
Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China.
Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Mol Cell Biochem. 2025 Feb;480(2):683-691. doi: 10.1007/s11010-024-05014-z. Epub 2024 May 8.
Despite enormous advances in the treatment of cardiovascular diseases, including I/R injury and heart failure, heart diseases remain a leading cause of mortality worldwide. Inositol-requiring enzyme 1 (IRE1) is an evolutionarily conserved sensor endoplasmic reticulum (ER) transmembrane protein that senses ER stress. It manages ER stress induced by the accumulation of unfolded/misfolded proteins via the unfolded protein response (UPR). However, if the stress still persists, the UPR pathways are activated and induce cell death. Emerging evidence shows that, beyond the UPR, IRE1 participates in the progression of cardiovascular diseases by regulating inflammation levels, immunity, and lipid metabolism. Here, we summarize the recent findings and discuss the potential therapeutic effects of IRE1 in the treatment of cardiovascular diseases.
尽管在心血管疾病（包括缺血/再灌注损伤和心力衰竭）的治疗方面取得了巨大进展，但心脏病仍然是全球主要的死亡原因。肌醇需要酶1（IRE1）是一种在进化上保守的内质网（ER）跨膜蛋白，可感知内质网应激。它通过未折叠蛋白反应（UPR）来处理由未折叠/错误折叠蛋白积累引起的内质网应激。然而，如果应激仍然持续，UPR途径就会被激活并诱导细胞死亡。新出现的证据表明，除了UPR之外，IRE1还通过调节炎症水平、免疫和脂质代谢参与心血管疾病的进展。在这里，我们总结了最近的研究发现，并讨论了IRE1在心血管疾病治疗中的潜在治疗作用。
