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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

IMPACT FACTOR increased in 2015: 3.017
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Source Normalized Impact per Paper (SNIP) 2015: 0.982
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Advanced glycation end-products induce endoplasmic reticulum stress in human aortic endothelial cells

Christos Adamopoulos1 / Elena Farmaki1 / Eliana Spilioti1 / Hippokratis Kiaris1 / 1 / Athanasios G. Papavassiliou1

1Department of Biological Chemistry, Medical School, University of Athens, Athens, Greece

Corresponding author: Assistant Professor Christina Piperi, PhD, Department of Biological Chemistry, Medical School, University of Athens, 75, M. Asias Street, 11527 Athens, Greece, Phone: +30 210 7462610, Fax: +30 210 8037372, E-mail:

Citation Information: Clinical Chemistry and Laboratory Medicine. Volume 52, Issue 1, Pages 151–160, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: 10.1515/cclm-2012-0826, March 2013

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Background: Advanced glycation end products (AGEs), the final products of the Maillard reaction, have been shown to impair endothelial proliferation and function, thus contributing to endothelial cell injury present in diabetes, inflammatory and cardiovascular diseases. Endoplasmic reticulum (ER) stress triggered under hyperglycemic, hypoxic and oxidative conditions has been implicated in endothelial dysfunction through activation of the unfolded protein response (UPR). The present study investigates the role of AGEs in ER stress induction in human aortic endothelial cells exposed to variable AGE treatments.

Methods: Human aortic endothelial cells (HAEC) were treated with increasing concentrations (100, 200 μg/mL) of AGE-bovine serum albumin (AGE-BSA) at different time-points (24, 48, 72 h). The induction of ER stress and the involved UPR components were investigated on mRNA and protein levels. Apoptosis was quantitatively determined by flow cytometry detecting propidium iodide expression and annexin V binding simultaneously.

Results: AGEs administration significantly reduced HAEC proliferation in a time- and dose-dependent manner. An immediate induction of the ER chaperones GRP78, GRP94 and the transcriptional activator, XBP-1 was observed at 24 h and 48 h. A later induction of the phospho-elF2α and proapoptotic transcription factor CHOP was observed at 48 h and 72 h, being correlated with elevated early apoptotic cell numbers at the same time-points.

Conclusions: The present study demonstrates that AGEs directly induce ER stress in human aortic endothelial cells, playing an important role in endothelial cell apoptosis. Targeting AGEs signaling pathways in order to alleviate ER stress may prove of therapeutic potential to endothelial dysfunction-related disorders.

Keywords: advanced glycation end-products (AGEs); apoptosis; endoplasmic reticulum (ER) stress; human aortic endothelial cells; unfolded protein response (UPR)

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