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DOI: 10.1055/s-0030-1255054
© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York
High Glucose Induces Dysfunction and Apoptosis in Endothelial Cells: Is the Effect of High Glucose Persistence more Important than Concentration?
Publication History
received 02.04.2010
first decision 02.04.2010
accepted 18.05.2010
Publication Date:
12 July 2010 (online)

Abstract
Oxidative stress and inflammation are involved in the pathogenesis of diabetic endothelial dysfunction. Herein we reported the biological changes induced by hyperglycemia in human umbilical vein endothelial cells (HUVECs) and the potential underlying mechanisms sought to determine whether high glucose concentration or the persistence plays a key role in the development of vascular lesions. The HUVECs were exposed to various glucose concentrations (5, 15, 30, and 60 mmol/L of D-glucose supplemented), and several oxidative stress factors, such as NO, NOS, and ROS, and inflammatory signaling markers, such as TNF-α, TNFR, RIP, TRADD, TRAF-2 and NF-κB, were analyzed at various times (24, 48, 72, and 96 h). High glucose (HG) induced a transient increase of NO within 24 h and decreased afterwards, in accord with the expression of eNOS. HG also increased ROS and TNF-α production and activated the TNF-α-mediated signal transduction, decreasing cell viability and inducing apoptosis. However, 3 HG groups had similar effects on HUVECs with the increased duration of exposure, which resulted in the amplified oxidative and inflammatory damage. Taken together, these findings suggest that the HG persistence exacerbates oxidative stress and activates the inflammatory-mediated signaling pathways, inducing endothelial dysfunction and apoptosis, regardless of the concentration of HG. Our results provide the first evidence that HG persistence is more important than concentration in the progress of diabetic endothelial dysfunction.
Key words
high glucose - endothelial cell - persistence - concentration
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Correspondence
S. WangPhD, MD
Vascular Surgery Institute
The First Affiliated Hospital
Sun Yat-Sen University
58 Zhongshan Erlu
510080 Guangzhou
People Republic of China
Phone: +86/20/8775 5766
Email: shenmingwang@vip.sohu.com