The Myocardial Unfolded Protein Response during Ischemic Cardiovascular Disease

Figure 1

Working model of the cardiomyocyte unfolded protein response during ischemia. Activators of the UPR in cardiomyocytes at the sarcoplasmic reticulum (SR)/endoplasmic reticulu (ER) include ischemia during cardiovascular disease. Proximal effectors of the UPR include IRE-1α, ATF6, and PERK. IRE-1α induces splicing of Xbp-1 mRNA and can promote prosurvival or proapoptotic pathways. ATF6 proteolysis leads to transcription of ER stress responsive genes and has been implicated in cardiomyocyte cell survival. Initial effects of PERK include translational arrest that reduces the load on the SR/ER folding machinery. Downstream and distal effector responses of PERK include CHOP, which promotes cardiomyocyte apoptosis and may contribute to heart failure.