Glycolaldehyde-derived advanced glycation end products (glycol-AGEs)-induced vascular smooth muscle cell dysfunction is regulated by the AGES-receptor (RAGE) axis in endothelium.
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.
a Department of Biotechnology , College of Life Science and Biotechnology, Korea University , Seoul , South Korea.
Mi-Hyun
MH
Nam
a Department of Biotechnology , College of Life Science and Biotechnology, Korea University , Seoul , South Korea.
Won-Rak
WR
Son
b Division of Biotechnology , College of Life Sciences and Biotechnology, Korea University , Seoul , South Korea.
Young Sik
YS
Lee
a Department of Biotechnology , College of Life Science and Biotechnology, Korea University , Seoul , South Korea.
Kwang-Won
KW
Lee
D000079:Acetaldehyde / Q000031:analogs & derivatives / Q000378:metabolism; D018920:Coculture Techniques; D004727:Endothelium / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000067759:Receptor for Advanced Glycation End Products; D015398:Signal Transduction / Q000187:drug effects
D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D048049:Extracellular Signal-Regulated MAP Kinases; D000079:Acetaldehyde; C010972:glycolaldehyde
Advanced glycation end-products; inflammatory cytokines; reactive oxygen species; vascular dysfunction