Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
Original Article
Effect of Advanced Glycation End Products on Lectin-Like Oxidized Low Density Lipoprotein Receptor-1 Expression in Endothelial Cells
Sammy WM ShiuYing WongKathryn CB Tan
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JOURNALS FREE ACCESS

2012 Volume 19 Issue 12 Pages 1083-1092

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Abstract

Aim: Lectin-like oxidized LDL receptor-1 (LOX-1) is a class E oxidized LDL specific scavenger receptor that recognizes multiple ligands. Advanced glycation end products (AGEs) have been recently identified as other ligands to LOX-1 and shown to increase LOX-1 expressions in diabetes; therefore, we investigated the underlying mechanism involved.
Methods: Confluent human aortic endothelial cells were treated with a fixed concentration of AGE-BSA or BSA as a control in the presence or absence of either antibody of the receptor for advanced glycation end products, mammalian target of rapamycin (mTOR) inhibitor rapamycin, NF-kB inhibitor, phosphoinositide 3-kinases (PI3K) inhibitor or anti-diabetic drug metformin. After stimulation, cells were lysed and Western blot protein expression on LOX-1, rapamycin-insensitive companion of mTOR (RICTOR), the phosphorylation status of p-mTOR, p-P70S6 kinase and p-Akt were determined.
Results: AGEs induced LOX-1 expression in endothelial cells. Pretreatment either with anti-RAGE antibody or LY294002 prior to AGE-BSA decreases LOX-1 and p-mTOR expressions. Incubating endothelial cells with AGE-BSA in the presence of rapamycin down-regulated the protein expression-level of p-mTOR by 41% (p<0.05) and LOX-1 expression by 61.5% (p<0.01). Knockdown of RICTOR by RNA silencing showed a 41.5% (p<0.01) and 71.2% (p<0.01) reduction in LOX-1 and p-Akt expressions, respectively. Preincubation of endothelial cells with AGE-BSA and metformin, an anti-diabetic drug known to have an mTOR inhibition effect, significantly reduced AGE-stimulated LOX-1 expression.
Conclusion: Our results indicated that LOX-1 up-regulation induced by AGE-BSA was a receptor mediated through RAGE and is via the PI3K/PDK1/mTORC2 pathway. Metformincan reduce AGE-stimulated LOX-1 expression in endothelial cells in vitro.

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この記事はクリエイティブ・コモンズ [表示 - 非営利 - 継承 4.0 国際]ライセンスの下に提供されています。
https://creativecommons.org/licenses/by-nc-sa/4.0/deed.ja
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