Endoplasmic reticulum stress contributes coronary artery dysfunction in type 2 diabetic mice (1086.7)

Abstract

Background: Vascular dysfunction is a major complication in type 2 diabetes. Although endoplasmic reticulum (ER) stress has been suggested to be a contributing factor in cardiovascular diseases, the relationship between ER stress and type 2 diabetic vascular dysfunction remains unclear. Thus, in the present study, we examined whether ER stress contributes coronary artery dysfunction and ER stress inhibition ameliorates vascular function in type 2 diabetes. Methods and Results: Type 2 diabetic and their control mice were treated with or without ER stress inhibitors (taurine‐conjugated ursodeoxycholic acid, TUDCA, and 4‐phenylbutyric acid, 4‐PBA) for 2 weeks. In type 2 diabetic mice, blood glucose, body weight, and insulin level are elevated compared to control mice. The myogenic response is potentiated and endothelium‐dependent relaxation is impaired in type 2 diabetic mice. Interestingly, treatment of ER stress inhibitors normalized myogenic responses and endothelium dependent relaxation.These data were associated with an increase in ER stress marker expression (CHOP, ATF6, XBP‐1, and phosphorylated‐eIF2α) in heart and mesenteric resistance arteries in type 2 diabetic mice, which were reduced by treatment with ER stress inhibitors. Conclusion: ER stress inhibition normalizes myogenic response and improves vascular function in type 2 diabetes. Therefore, ER stress could be a potential target for cardiovascular diseases in diabetes mellitus.Grant Funding Source: supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF)