Nogo-A Mediated Endoplasmic Reticulum Stress During Myocardial Ischemic-Reperfusion Injury in Diabetic Rats

Among the three isoforms encoded by neurite outgrowth inhibitor proteins has been intensely investigated as a central nervous system inhibitor. Although neurite outgrowth inhibitor protein-A (Nogo-A) expression is increased in plasma of patients who have experienced a coronary heart disease, its role in heart disease is not well elucidated. In this study, we discovered a significant increase in Nogo-A expression in diabetic myocardial ischemia reperfusion (MI/R) injury conditions. Accelerated Nogo-A and MI/R injury in diabetic rats was attenuated by tauroursodeoxycholic acid treatment and knockdown of Nogo-A per se is sufficient to decrease endoplasmic reticulum (ER) stress as well as prevents cardiomyocyte apoptosis. We hypothesized that decreased Nogo-A levels might reducing diabetic MI/R injury. Nogo-A interacted with C/EBP homologous protein, suggesting a role for Nogo-A in ER stress during diabetic MI/R. In conclusion, Nogo-A mediated ER stress plays a major role in diabetic MI/R injury, and pathologically altered Nogo-A expression mediates diabetic MI/R injury, suggesting Nogo-A as a novel target for the treatment of diabetic MI/R injury in clinical settings.