Information de reference pour ce titreAccession Number: | 00004686-199509000-00028.
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Author: | Schmidt, Ann Marie; Hori, Osamu; Chen, Jing Xian; Li, Jian Feng; Crandall, Jill; Zhang, Jinghua; Cao, Rong; Yan, Shi Du; Brett, Jerold; Stern David
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Institution: | Departments of Medicine and Physiology, Columbia University-College of Physicians and Surgeons, New York 10032 Address correspondence to Dr. Ann Marie Schmidt, Department of Medicine, P & S 11-518, Columbia University-College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032. Phone: 212-305-1615; FAX: 212-305-5337. J. Crandall's present address is Department of Medicine, Joslin Center for Diabetes, St. Luke's-Roosevelt Hospital, New York, NY, 10019. Received for publication 13 January 1995 and accepted in revised form 9 May 1995.
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Title: | Advanced Glycation Endproducts Interacting with Their Endothelial Receptor Induce Expression of Vascular Cell Adhesion Molecule-1 (VCAM-1) in Cultured Human Endothelial Cells and in Mice: A Potential Mechanism for the Accelerated Vasculopathy of Diabetes.[Article]
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Source: | Journal of Clinical Investigation. 96(3):1395-1403, September 1995.
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Abstract: | Vascular cell adhesion molecule-1 (VCAM-1), an inducible cell-cell recognition protein on the endothelial cell surface (EC), has been associated with early stages of atherosclerosis. In view of the accelerated vascular disease observed in patients with diabetes, and the enhanced expression of VCAM-1 in diabetic rabbits, we examined whether irreversible advanced glycation endproducts (AGEs), could mediate VCAM-1 expression by interacting with their endothelial cell receptor (receptor for AGE, RAGE). Exposure of cultured human ECs to AGEs induced expression of VCAM-1, increased adhesivity of the monolayer for Molt-4 cells, and was associated with increased levels of VCAM-1 transcripts. The inhibitory effect of anti-RAGE IgG, a truncated form of the receptor (soluble RAGE) or N-acetylcysteine on VCAM-1 expression indicated that AGE-RAGE-induced oxidant stress was central to VCAM-1 induction. Electrophoretic mobility shift assays on nuclear extracts from AGE-treated ECs showed induction of specific DNA binding activity for NF-kB in the VCAM-1 promoter, which was blocked by anti-RAGE IgG or N-acetylcysteine. Soluble VCAM-1 antigen was elevated in human diabetic plasma. These data are consistent with the hypothesis that AGE-RAGE interaction induces expression of VCAM-1 which can prime diabetic vasculature for enhanced interaction with circulating monocytes. (J. Clin. Invest. 1995. 96:1395-1403.) Key words: hyperglycemia centered dot atherosclerosis centered dot adhesion molecule centered dot endothelium centered dot oxidation
Copyright (C) 1995 The American Society for Clinical Investigation, Inc.
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Language: | English.
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Document Type: | Articles.
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Journal Subset: | Clinical Medicine. Life Sciences.
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ISSN: | 0021-9738
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NLM Journal Code: | hs7, 7802877
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Annotation(s) | |
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