ER stress inhibition improves coronary artery function in type 2 diabetic mice

Aim: 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 vascular dysfunction in type 2 diabetes 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: Type 2 diabetic and their control mice were treated with or without ER stress inhibitor (taurine-conjugated ursodeoxycholic acid, TUDCA, 150 mg kg⁻¹ day⁻¹, intra-peritoneal injection for two weeks) for 2 weeks. Myogenic response and endothelium-dependent relaxation were measured in the pressurized coronary arteries. Results In type 2 diabetic mice, blood glucose, and body weight are elevated compared to control mice. The myogenic response is potentiated and endothelium-dependent relaxation is impaired in the coronary arteries from type 2 diabetic mice. Interestingly, treatment of ER stress inhibitor normalized myogenic responses and endothelium-dependent relaxation. These data were associated with an increase in ER stress marker expression or phosphorylation (IRE1-XBP-1, and PERK-eIF2α) in type 2 diabetic mice, which were reduced by treatment with ER stress inhibitor. 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.

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