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

Abstract EN

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 (PPARγ) expression was restored by salusin-β shRNA, and PPARγ 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.