title: Inhibition of endoplasmic reticulum stress improves coronary artery function in type 2 diabetic mice.
abstract: What is the central question of this study? Endoplasmic reticulum (ER) stress has been reported to be involved in type 2 diabetes; however, the role of exacerbated ER stress in vascular dysfunction in type 2 diabetes remains unknown. What is the main finding and its importance? The main findings of this study are that ER stress is increased in the coronary arteries in type 2 diabetes, and inhibition of ER stress using taurine-conjugated ursodeoxycholic acid improves vascular function, which is associated with normalization of the myogenic response and endothelium-dependent relaxation. Vascular dysfunction is a major complication in type 2 diabetes. Although endoplasmic reticulum (ER) stress has been suggested to be a contributory 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 to coronary artery dysfunction and whether inhibition of ER stress ameliorates vascular function in type 2 diabetes. Type 2 diabetic mice and their control counterparts were treated with an ER stress inhibitor (taurine-conjugated ursodeoxycholic acid, 150 mg kg(-1)  day(-1) , by i.p. injection) for 2 weeks or not treated. The myogenic response and endothelium-dependent relaxation were measured in pressurized coronary arteries. In type 2 diabetic mice, blood glucose and body weight were elevated compared with control mice. The myogenic response was potentiated and endothelium-dependent relaxation impaired in coronary arteries from the type 2 diabetic mice. Interestingly, treatment with the ER stress inhibitor normalized the 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 the ER stress inhibitor. Inhibition of ER stress normalizes the myogenic response and improves vascular function in type 2 diabetes. Therefore, ER stress could be a potential target for cardiovascular diseases in diabetes mellitus.
authors.affiliation: Department of Physiology, College of Medicine, Brain Korea 21 Plus Project for Medical Sciences, Yonsei University, Seoul, Korea.
authors.forename: Soo-Kyoung
authors.initials: SK
authors.lastname: Choi
authors.affiliation: Department of Physiology, College of Medicine, Brain Korea 21 Plus Project for Medical Sciences, Yonsei University, Seoul, Korea.
authors.forename: Mihwa
authors.initials: M
authors.lastname: Lim
authors.affiliation: Department of Physiology, College of Medicine, Brain Korea 21 Plus Project for Medical Sciences, Yonsei University, Seoul, Korea.
authors.forename: Soo-In
authors.initials: SI
authors.lastname: Yeon
authors.affiliation: Department of Physiology, College of Medicine, Brain Korea 21 Plus Project for Medical Sciences, Yonsei University, Seoul, Korea.
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Lee
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D003331:Coronary Vessels / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004721:Endoplasmic Reticulum / Q000502:physiology*; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D004730:Endothelium, Vascular / Q000503:physiopathology; D008297:Male; D051379:Mice; D010766:Phosphorylation / Q000502:physiology
chemical_list: D001786:Blood Glucose