Abstract
Advanced glycation end-products (AGEs) are involved in the development of vascular smooth muscle cell (VSMC) dysfunction and the progression of atherosclerosis. However, AGEs may indirectly affect VSMCs via AGEs-induced signal transduction between monocytes and human umbilical endothelial cells (HUVECs), rather than having a direct influence. This study was designed to elucidate the signaling pathway underlying AGEs-RAGE axis influence on VSMC dysfunction using a co-culture system with monocytes, HUVECs and VSMCs. AGEs stimulated production of reactive oxygen species and pro-inflammatory mediators such as tumor necrosis factor-α and interleukin-1β via extracellular-signal-regulated kinases phosphorylation and nuclear factor-κB activation in HUVECs. It was observed that AGEs-induced pro-inflammatory cytokines increase VSMC proliferation, inflammation and vascular remodeling in the co-culture system. This result implies that RAGE plays a role in AGEs-induced VSMC dysfunction. We suggest that the regulation of signal transduction via the AGEs-RAGE axis in the endothelium can be a therapeutic target for preventing atherosclerosis.
Original language | English |
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Pages (from-to) | 67-78 |
Number of pages | 12 |
Journal | Cell Communication and Adhesion |
Volume | 22 |
Issue number | 2-6 |
DOIs | |
Publication status | Published - 2015 Nov 2 |
Bibliographical note
Funding Information:This work was supported by Korea University Grant [K1516071].
Publisher Copyright:
© 2016 Informa UK Limited, trading as Taylor & Francis Group.
Keywords
- Advanced glycation end-products
- inflammatory cytokines
- reactive oxygen species
- vascular dysfunction
ASJC Scopus subject areas
- Clinical Biochemistry
- Cell Biology