The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
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.
Open accessAbstract
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.
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“Excessive AGE formation is particularly associated with cross-linking of matrix proteins such as collagen, vitronectin, and laminin.[2,10,11]”
From The Role of Dietary Advanced Glycation End Products in Metabolic Dysfunction (2021) · cites this paper as [11]
In the citing paper
“Binding of AGEs to the receptor for AGE (RAGE) enhances the expression of adhesion molecules on endothelial cells to promote the migration and differentiation of monocytes into macrophages.”
From The Vasculature in Prediabetes (2018) · cites this paper as [60]
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Cites
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Role of Oxidative Stress in Development of Complications in Diabetes
Baynes, J. (1991) · Diabetes · doi:10.2337/diab.40.4.405 · Cited by 3,791
Advanced Glycosylation End Products in Tissue and the Biochemical Basis of Diabetic Complications
Flier, J. S., Underhill, L. H., Brownlee, M., Cerami, A., & Vlassara, H. (1988) · New England Journal of Medicine · doi:10.1056/nejm198805193182007 · Cited by 2,512
Endothelial Expression of a Mononuclear Leukocyte Adhesion Molecule During Atherogenesis
Cybulsky, M. I., & Gimbrone, M. A. (1991) · Science · doi:10.1126/science.1990440 · Cited by 1,710
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Self-citationYan, S. D., Schmidt, A. M., Anderson, G. M., Zhang, J., Brett, J., Zou, Y., Pinsky, D. J., & Stern, D. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)36966-1 · Cited by 1,305
Self-citationCytokines and endothelial cell biology
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Cited by
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Biochemistry and molecular cell biology of diabetic complications
Brownlee, M. (2001) · Nature · doi:10.1038/414813a · Cited by 9,107
Oxidative stress and diabetic complications
Giacco, F., & Brownlee, M. (2010) · Circulation Research · doi:10.1161/circresaha.110.223545 · Cited by 5,461
The Pathobiology of Diabetic Complications
Brownlee, M. (2005) · Diabetes · doi:10.2337/diabetes.54.6.1615 · Cited by 5,339
The Free Radical Theory of Aging Matures
BECKMAN, K. B., & AMES, B. N. (1998) · Physiological Reviews · doi:10.1152/physrev.1998.78.2.547 · Cited by 3,879
Mechanisms of Diabetic Complications
Forbes, J. M., & Cooper, M. E. (2013) · Physiological Reviews · doi:10.1152/physrev.00045.2011 · Cited by 2,890
“Its physiological role is thought to be an amplification of immune and inflammatory responses, given that RAGE is highly expressed on mucous membranes (45, 523).”
Background
Metadata
- Authors
- Schmidt, A. M., Hori, O., Chen, J. X., Li, J. F., Crandall, J., Zhang, J., Cao, R., Yan, S. D., Brett, J., & Stern, D.
- Affiliations
- Columbia University Irving Medical Center (US)
- Columbia University (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1995-09-01
- Volume
- 96
- Issue
- 3
- Pages
- 1395-1403
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC185762
- OpenAlex
- W2138928713
- Cited by
- 896
- References
- 43
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 15 · 2023: 16 · 2022: 13 · 2021: 21 · 2020: 16 · 2019: 23 · 2018: 16 · 2017: 26 · 2016: 17 · 2015: 34 · 2014: 32 · 2013: 35 · 2012: 36
- FWCI
- 17.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- KU ScholarWorks (University of Kansas) (submittedVersion, other-oa)
- Funders
- American Heart Association
- National Institutes of Health (5r01hl042833-10, 5p50hl021006-17)
- U.S. Public Health Service
- National Institute on Aging (AG00602)
- National Heart, Lung, and Blood Institute (HL-42833, HL 21006)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Keywords
- advanced glycation end products, receptor for advanced glycation end products, VCAM-1, endothelial cells, diabetes mellitus, diabetic vascular disease, oxidative stress, NF-kB, soluble RAGE, N-acetylcysteine, monocyte adhesion, atherosclerosis, soluble VCAM-1
- MeSH terms
- Receptor for Advanced Glycation End Products, Animals, Base Sequence, Cell Adhesion, Cell Line, Cell Nucleus, Cells, Cultured, Diabetic Angiopathies, Endothelium, Vascular, Enzyme-Linked Immunosorbent Assay, Humans, Male, Models, Biological, Molecular Sequence Data, Receptors, Immunologic, Transcription, Genetic, Umbilical Veins, Cell Adhesion Molecules, Gene Expression, Polymerase Chain Reaction, Glycation End Products, Advanced, DNA Primers, Oxidative Stress, Vascular Cell Adhesion Molecule-1, Mice
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