Salusin-β Is Involved in Diabetes Mellitus-Induced Endothelial Dysfunction via Degradation of Peroxisome Proliferator-Activated Receptor Gamma. (19th November 2017)

• Record Type: Journal Article
• Authors: Sun, Hai-Jian; Chen, Dan; Wang, Pei-Yao; Wan, Ming-Yu; Zhang, Chen-Xing; Zhang, Zhi-Xuan; Lin, Wei; Zhang, Feng
• Other Names: Kelley Eric E. Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2017(2017)
• Publication Date: 2017-11-19
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2017/6905217
• Languages: English
• ISSNs: 1942-0900

Abstract

Abstract : The pathophysiological mechanisms for vascular lesions in diabetes mellitus (DM) are complex, among which endothelial dysfunction plays a vital role. Therapeutic target against endothelial injury may provide critical venues for treatment of diabetic vascular diseases. We recently identified that salusin- β contributed to high glucose-induced endothelial cell apoptosis. However, the roles of salusin- β in DM-induced endothelial dysfunction remain largely elusive. Male C57BL/6J mice were used to induce type 2 diabetes mellitus (T2DM) model. Human umbilical vein endothelial cells (HUVECs) were cultured in high glucose/high fat (HG/HF) medium. We demonstrated increased expression of salusin- β in diabetic aortic tissues and high-glucose/high-fat- (HG/HF-) incubated HUVECs. Disruption of salusin- β by shRNA abrogated the reactive oxygen species (ROS) production, inflammation, and nitrotyrosine content of HUVECs cultured in HG/HF medium. The HG/HF-mediated decrease in peroxisome proliferator-activated receptor γ (PPAR γ ) expression was restored by salusin- β shRNA, and PPAR γ inhibitor T0070907 abolished the protective actions of salusin- β shRNA on endothelial injury in HG/HF-treated HUVECs. Salusin- β silencing obviously improved endothelium-dependent vasorelaxation, oxidative stress, inflammatory response, and nitrative stress in diabetic aorta. Taken together, our results highlighted the essential role of salusin- β in pathological endothelial dysfunction, and salusin- β may be a promising target in treatment of vascular complications of DM.