TRAF6 mediates high glucose-induced endothelial dysfunction
- Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Rd, Shanghai 200233 (China)
- Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Rd, Shanghai 200233 (China)
- Shanghai Jiao Tong University School of Medicine, 227 Chongqing Rd, Shanghai 200025 (China)
- Department of Endocrinology and Metabolism, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai Clinical Medical Centre of Diabetes, Shanghai Key Laboratory of Diabetes, Shanghai Key Clinical Centre of Metabolic Diseases, Shanghai Institute for Diabetes, 600 Yishan Rd, Shanghai 200233 (China)
Highlights: • TRAF6 mediated high glucose-induced endothelial dysfunction. • NF-κB- and AP-1-dependent signaling served as mechanism. • Targeting TRAF6 may delay progression of vascular diseases during diabetes mellitus and atherosclerosis. To investigate the role of tumor necrosis factor-associated factor 6 (TRAF6) in high glucose-induced endothelial cell dysfunction. Human aortic endothelial cells (HAECs) were cultured in high glucose medium, and TRAF6 expression was assayed by quantitative real-time Polymerase Chain Reaction (PCR) and western blotting. The effect of TRAF6 on in vitro endothelial cell viability, apoptosis, migration, and endothelial–monocyte adhesion was investigated by gene knockdown. The expression of TRAF6 and related adhesion molecules was assayed in a mouse streptozotocin-induced type I diabetes model. The signaling pathways associated with TRAF6 effects on endothelial cells were investigated in high glucose HAEC cultures. Culture of HAECs in high glucose medium significantly increased TRAF6 mRNA and protein expression in a time dependent manner. High glucose markedly reduced HAEC viability, apoptosis, and migration, and these effects was significantly reversed by TRAF6 knockdown. High glucose significantly increased intercellular adhesion of THP-1 monocytic cells and HAECs via upregulation of ICAM-1 and VCAM-1 expression, and TRAF6 knockdown attenuated the effect on THP-1 cell adhesion. TRAF6, ICAM-1, and VCAM-1 expression were increased in aorta tissue of mice with streptozotocin-induced diabetes. The free radical scavenger N-acetyl-L-cysteine attenuated TRAF6 expression in HAECs cultured in high glucose medium, and TRAF6 knockdown inhibited high glucose-induced IκB-α degradation and JNK phosphorylation. TRAF6 mediated high glucose-induced endothelial dysfunction via NF-κB- and AP-1-dependent signaling. Targeting TRAF6 may delay progression of vascular diseases during diabetes mellitus and atherosclerosis.
- OSTI ID:
- 23082627
- Journal Information:
- Experimental Cell Research, Vol. 370, Issue 2; Other Information: Copyright (c) 2018 Published by Elsevier Inc.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
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