Salusin-beta Is Involved in Diabetes Mellitus-Induced Endothelial Dysfunction via Degradation of Peroxisome Proliferator-Activated Receptor Gamma

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-beta contributed to high glucose-induced endothelial cell apoptosis. However, the roles of salusin-beta 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-beta in diabetic aortic tissues and high-glucose/high-fat- (HG/HF-) incubated HUVECs. Disruption of salusin-beta 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 gamma (PPAR gamma) expression was restored by salusin-beta shRNA, and PPAR. inhibitor T0070907 abolished the protective actions of salusin-beta shRNA on endothelial injury in HG/HF-treated HUVECs. Salusin-beta 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-beta in pathological endothelial dysfunction, and salusin-beta may be a promising target in treatment of vascular complications of DM.