Cited by 896Advanced Glycation End Products researchCell Adhesion Molecules ResearchNitric Oxide and Endothelin Effects

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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.

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Schmidt, A M, Hori, O, Chen, J X, Li, J F, Crandall, J, Zhang, J, Cao, R, Yan, S D, Brett, J, Stern, D·1995·Journal of Clinical Investigation

DOI 10.1172/jci118175PMC PMC185762

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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.

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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)
ORCID: Hori, O
Crandall, J
Zhang, J
Cao, R
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1995-09-01
Volume: 96
Issue: 3
Pages: 1395-1403
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci118175
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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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.

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