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AGEs‐induced pro‐atherosclerosis pathway: endothelium are regulated by the AGEs‐RAGE axis (832.12)
Author(s) -
Nam MiHyun,
Hong ChungOui,
Koo YunChang,
Lee KwangWon
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.832.12
Subject(s) - rage (emotion) , glycation , microbiology and biotechnology , chemistry , cytokine , endothelium , proinflammatory cytokine , gene knockdown , receptor , signal transduction , inflammation , oxidative stress , immunology , medicine , biology , apoptosis , biochemistry , neuroscience
During hyperglycemia, reducing sugars react with the amino groups of proteins non‐enzymatically to form Schiff base and Amadori products, which undergo formation of advanced glycation end‐products (AGEs). Binding AGEs and receptor for AGEs (RAGE) generated oxidative stress and several vascular cells triggered secretion of inflammatory cytokine and abnormal signal transduction but the underlying mechanism remains unclear. We evaluate the hypothesis that the AGEs‐RAGE axis might mediate combined signals contributed to the local regulations in co‐cultures of human monocytes (THP‐1), endothelial cells (HUVEC) and aortic vascular smooth muscle cell (SMC). The results revealed that production of reactive oxygen species (ROS) and adhesion of monocytes to endothelium induced AGEs were decreased by RAGE knockdown HUVEC. We further discovered that TNF‐α and IL‐1β as pro‐inflammatory cytokines were markedly suppressed in AGEs‐stimulated HUVECs and THP‐1 simultaneously knockdown of RAGE. Besides, SMC were down‐regulated inflammatory cytokines and decreased proliferation in co‐culture system. In conclusion, AGEs stimulation of vascular cells causes binding of RAGE, enhances the production of ROS, adhesion of monocytes, and expression of cytokines eventually contributes to the progression of atherosclerosis.