BACKGROUND/AIMS: Endoplasmic reticulum (ER) stress has emerged as a potential mechanism contributing to diabetes and its comorbidities. However, the importance of ER stress in diabetic vascular dysfunction is unclear. The purpose of this study was to examine the effects of the ER stress inhibitor, tauroursodeoxycholic acid (TUDCA), on arterial stiffness and endothelial dysfunction in type 2 diabetic mice. METHODS: Carotid and mesenteric artery endothelial function were assessed via ex vivo pressure myography, and arterial stiffness was measured by aortic pulse wave velocity. The effects of TUDCA were examined both acutely (ex vivo) and chronically (250 mg/kg/day; i.p., 4 weeks). RESULTS: Compared to control C57BL/6J mice, db/db (DB) mice did not display carotid artery endothelial dysfunction; however, mesenteric artery endothelial function was markedly impaired. Acute incubation and chronic administration of TUDCA improved endothelium-dependent dilation in DB mesenteric arteries, without affecting endothelium-independent dilation. Chronic TUDCA administration also reduced arterial stiffness and was associated with reductions in ER stress markers in aortic and perivascular adipose tissue. CONCLUSIONS: These results suggest that ER stress may represent a novel cause of, and therapeutic target for, diabetic vascular dysfunction.
BACKGROUND/AIMS: Endoplasmic reticulum (ER) stress has emerged as a potential mechanism contributing to diabetes and its comorbidities. However, the importance of ER stress in diabetic vascular dysfunction is unclear. The purpose of this study was to examine the effects of the ER stress inhibitor, tauroursodeoxycholic acid (TUDCA), on arterial stiffness and endothelial dysfunction in type 2 diabeticmice. METHODS: Carotid and mesenteric artery endothelial function were assessed via ex vivo pressure myography, and arterial stiffness was measured by aortic pulse wave velocity. The effects of TUDCA were examined both acutely (ex vivo) and chronically (250 mg/kg/day; i.p., 4 weeks). RESULTS: Compared to control C57BL/6J mice, db/db (DB) mice did not display carotid artery endothelial dysfunction; however, mesenteric artery endothelial function was markedly impaired. Acute incubation and chronic administration of TUDCA improved endothelium-dependent dilation in DB mesenteric arteries, without affecting endothelium-independent dilation. Chronic TUDCA administration also reduced arterial stiffness and was associated with reductions in ER stress markers in aortic and perivascular adipose tissue. CONCLUSIONS: These results suggest that ER stress may represent a novel cause of, and therapeutic target for, diabetic vascular dysfunction.
Authors: Dustin M Lee; Kayl E Ecton; S Raj J Trikha; Scott D Wrigley; Keely N Thomas; Micah L Battson; Yuren Wei; Sarah A Johnson; Tiffany L Weir; Christopher L Gentile Journal: Am J Physiol Gastrointest Liver Physiol Date: 2020-05-18 Impact factor: 4.052
Authors: Micah L Battson; Dustin M Lee; Lance C Li Puma; Kayl E Ecton; Keely N Thomas; Hallie P Febvre; Adam J Chicco; Tiffany L Weir; Christopher L Gentile Journal: Am J Physiol Heart Circ Physiol Date: 2019-09-27 Impact factor: 4.733
Authors: Dustin M Lee; Micah L Battson; Dillon K Jarrell; Shuofei Hou; Kayl E Ecton; Tiffany L Weir; Christopher L Gentile Journal: Cardiovasc Diabetol Date: 2018-04-27 Impact factor: 9.951
Authors: Dustin M Lee; Kyle J Sevits; Micah L Battson; Yuren Wei; Kimberly A Cox-York; Christopher L Gentile Journal: PLoS One Date: 2019-12-31 Impact factor: 3.240