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

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 (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.

• Authors: Hai-Jian Sun, Dan Chen, Pei-Yao Wang, Ming-Yu Wan, Chen-Xing Zhang, Zhi-Xuan Zhang, Wei Lin, Feng Zhang
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2017 Pg. 6905217 ( 2017) ISSN: 1942-0994 [Electronic] United States
• PMID: 29359008 (Publication Type: Journal Article)

Chemical References

• Intercellular Signaling Peptides and Proteins
• NF-kappa B
• PPAR gamma
• Reactive Oxygen Species
• TOR2A protein, human

Topics

• Animals
• Diabetes Mellitus, Experimental (complications, metabolism, pathology)
• Diabetes Mellitus, Type 2 (complications, metabolism, pathology)
• Diet, High-Fat (adverse effects)
• Human Umbilical Vein Endothelial Cells (metabolism, pathology)
• Humans
• Intercellular Signaling Peptides and Proteins (chemistry, genetics, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• NF-kappa B (metabolism)
• Oxidative Stress
• PPAR gamma (metabolism)
• Reactive Oxygen Species (metabolism)
• Vascular Diseases (etiology, metabolism, pathology)