The Laboratory of Translational Medicine, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, People's Republic of China.
Department of Clinical Medicine, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, People's Republic of China.
Mol Cell Biochem. 2024 May;479(5):1079-1092. doi: 10.1007/s11010-023-04780-6. Epub 2023 Jun 13.
Inositol requiring enzyme 1 (IRE1) is generally thought to control the most conserved pathway in the unfolded protein response (UPR). Two isoforms of IRE1, IRE1α and IRE1β, have been reported in mammals. IRE1α is a ubiquitously expressed protein whose knockout shows marked lethality. In contrast, the expression of IRE1β is exclusively restricted in the epithelial cells of the respiratory and gastrointestinal tracts, and IRE1β-knockout mice are phenotypically normal. As research continues to deepen, IRE1α was showed to be tightly linked to inflammation, lipid metabolism regulation, cell death and so on. Growing evidence also suggests an important role for IRE1α in promoting atherosclerosis (AS) progression and acute cardiovascular events through disrupting lipid metabolism balance, facilitating cells apoptosis, accelerating inflammatory responses and promoting foam cell formation. In addition, IRE1α was recognized as novel potential therapeutic target in AS prevention. This review provides some clues about the relationship between IRE1α and AS, hoping to contribute to further understanding roles of IRE1α in atherogenesis and to be helpful for the design of novel efficacious therapeutics agents targeting IRE1α-related pathways.
肌醇需求酶 1（IRE1）通常被认为控制未折叠蛋白反应（UPR）中最保守的途径。哺乳动物中已经报道了两种 IRE1 同工型，IRE1α 和 IRE1β。IRE1α 是一种广泛表达的蛋白质，其敲除表现出明显的致死性。相比之下，IRE1β 的表达仅局限于呼吸道和胃肠道的上皮细胞中，而 IRE1β 敲除小鼠表型正常。随着研究的不断深入，IRE1α 被证明与炎症、脂质代谢调节、细胞死亡等密切相关。越来越多的证据表明，IRE1α 通过破坏脂质代谢平衡、促进细胞凋亡、加速炎症反应和促进泡沫细胞形成，在促进动脉粥样硬化（AS）进展和急性心血管事件中发挥重要作用。此外，IRE1α 被认为是 AS 预防的新型潜在治疗靶点。本综述提供了一些关于 IRE1α 与 AS 之间关系的线索，希望有助于进一步了解 IRE1α 在动脉粥样形成中的作用，并有助于设计针对 IRE1α 相关途径的新型有效治疗药物。
