Role of IRE1 cascade mediated by endoplasmic reticulum stress in atherosclerosis

The unfolded protein response is the most thorough study of signaling pathways among endoplasmic reticulum stress at present. Numerous studies have shown that the unfolded protein response mediates vascular cell death and plaque instability, which are closely related to clinical progression of atherosclerosis. Inositol-requiring enzyme 1 (IRE1) is an evolutionarily most-conserved endoplasmic reticulum transmembrane sensor of the unfolded protein response. IRE1 activation may mediate the functional spliced XBP1 production or JNK translational activation, and then activate downstream signaling pathways. IRE1 cascade is involved in the physiological and pathological processes of atherosclerosis. Here we review the effect of IRE1 cascade mediated by endoplasmic reticulum stress on the arterial wall endothelial cells, vascular smooth muscle cells and macrophages structure and function, and summarize the role of IRE1-XBP1 pathway and IRE1-JNK pathway in development of atherosclerosis and vulnerable plaque formation.