IRE1α: from the function to the potential therapeutic target in atherosclerosis

Inositol requiring enzyme 1 (IRE1) is generally thought to control the most conserved pathway in the unfolded protein response (UPR). Two isoforms of IRE1, IRE1 alpha and IRE1 beta, have been reported in mammals. IRE1 alpha is a ubiquitously expressed protein whose knockout shows marked lethality. In contrast, the expression of IRE1 beta is exclusively restricted in the epithelial cells of the respiratory and gastrointestinal tracts, and IRE1 beta-knockout mice are phenotypically normal. As research continues to deepen, IRE1 alpha was showed to be tightly linked to inflammation, lipid metabolism regulation, cell death and so on. Growing evidence also suggests an important role for IRE1 alpha 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, IRE1 alpha was recognized as novel potential therapeutic target in AS prevention. This review provides some clues about the relationship between IRE1 alpha and AS, hoping to contribute to further understanding roles of IRE1 alpha in atherogenesis and to be helpful for the design of novel efficacious therapeutics agents targeting IRE1 alpha-related pathways.