ABSTRACT
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 IRE1ß, have been reported in mammals. IRE1α is a ubiquitously expressed protein whose knockout shows marked lethality. In contrast, the expression of IRE1ß is exclusively restricted in the epithelial cells of the respiratory and gastrointestinal tracts, and IRE1ß-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.
ABSTRACT
Irisin, a novel exercise-induced myokine, has been shown to play important roles in increasing white adipose tissue browning, regulating energy metabolism and improving insulin resistance. Growing evidence suggests a direct role for irisin in preventing atherosclerosis (AS) by inhibiting oxidative stress, improving dyslipidemia, facilitating anti-inflammation, reducing cellular damage and recovering endothelial function. In addition, some studies have noted that serum irisin levels play an essential role in cardiovascular diseases (CVDs) risk prediction, highlighting that irisin has the potential to be a useful predictive marker and therapeutic target of AS, especially in monitoring therapeutic efficacy. This review summarizes the understanding of irisin-mediated regulation in essential biological pathways and functions in atherosclerosis and prompts further exploitation of the biological properties of irisin in the pathogenesis of atherosclerosis.
