High glucose-induced apoptosis in human coronary artery endothelial cells involves up-regulation of death receptors

Cardiovascular Diabetology

Original Investigation

Shun-ichiro Kageyama¹  Seiji Yamamoto¹  Yuichi Hattori¹  Ryo Uchimido¹  Naoyuki Matsuda¹  Hiroki Yokoo¹  Kengo Tomita¹  Natsuko Kageyama-Yahara² 

[1] Department of Molecular and Medical Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 930-0194, Toyama, Japan;Division of Gastrointestinal Pathophysiology, Department of Bioscience, Institute of Natural Medicine, University of Toyama, 930-0194, Toyama, Japan;

关键词: High Glucose;    Death Receptor;    Diabetic Mouse;    Endothelial Cell Apoptosis;    High Glucose Condition;   

DOI  :  10.1186/1475-2840-10-73

 received in 2011-04-22, accepted in 2011-08-04,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundHigh glucose can induce apoptosis in vascular endothelial cells, which may contribute to the development of vascular complications in diabetes. We evaluated the role of the death receptor pathway of apoptotic signaling in high glucose-induced apoptosis in human coronary artery endothelial cells (HCAECs).MethodsHCAECs were treated with media containing 5.6, 11.1, and 16.7 mM of glucose for 24 h in the presence or absence of tumor necrosis factor (TNF)-α. For detection of apoptosis, DNA fragmentation assay was used. HCAEC expression of death receptors were analyzed by the PCR and flow cytometry methods. Also, using immunohistochemical techniques, coronary expression of death receptors was assessed in streptozotocin-nicotinamide-induced type 2 diabetic mice.ResultsExposure of HCAECs to high glucose resulted in a significant increase in TNF-R1 and Fas expression, compared with normal glucose. High glucose increased TNF-α production by HCAECs and exogenous TNF-α up-regulated TNF-R1 and Fas expression in HCAECs. High glucose-induced up-regulation of TNF-R1 and Fas expression was undetectable in the presence of TNF-α. Treatment with TNF-R1 neutralizing peptides significantly inhibited high glucose-induced endothelial cell apoptosis. Type 2 diabetic mice displayed appreciable expression of TNF-R1 and Fas in coronary vessels.ConclusionsIn association with increased TNF-α levels, the death receptors, TNF-R1 and Fas, are up-regulated in HCAECs under high glucose conditions, which could in turn play a role in high glucose-induced endothelial cell apoptosis.

【 授权许可】

Unknown   
© Kageyama et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.