Exp Clin Endocrinol Diabetes 2011; 119(4): 225-233
DOI: 10.1055/s-0030-1255054
Article

© 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?

Y. Zhang1 , H. Shi2 , G. Sun2 , S. Li2 , X. Xu1 , C. Ye1 , X. Li1 , S. Wang1
  • 1Vascular Surgery Institute, Department of Vascular Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China
  • 2Department of General Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China
Further Information

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.

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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

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