Advanced glycation end products impair the functions of saphenous vein but not thoracic artery smooth muscle cells through RAGE/MAPK signalling pathway in diabetes.
Saphenous vein (SV) and internal thoracic artery (ITA) are commonly used bypass conduits. However, graft failure occurs in SV rather than in ITA, especially in diabetes (DM). The mechanism for this difference has not been fully understood. Accumulation of advanced glycation end products (AGEs) and activation of AGEs receptor (RAGE) could accelerate smooth muscle cells (SMC) proliferation in DM, we thus asked whether AGEs-RAGE could mediate the differences between SMC from SV (SMCV ) and from ITA (SMCA ). Twenty-five patients with DM and other 25 patients without DM were enclosed in DM and control group, respectively. AGEs (100 μg/ml) were added to cultured SMCA and SMCV obtained at coronary artery bypass graft (CABG) and proliferative rates were determined. Transcript expression, phosphorylation or protein expression levels of MAP kinase family (ERK, p38 and JNK), matrix metalloproteinases (MMP)-2 and MMP-9 were analysed by real-time PCR, Western-blot or immunofluorescence staining, respectively. Compared with paired SMCA , SMCV showed significantly increased proliferation rate, MAP kinase family phosphorylation, and MMP-2/9 expression in both groups, especially in DM group. The responses of SMCV induced by AGEs were significantly larger in DM than in control group, which could be suppressed by inhibition of RAGE and ERK. However, all the cellular events of SMCV were not found in paired SMCA . This study suggests that AGEs-RAGE could induce the proliferation of SMCV but not SMCA via MAP kinase pathway in DM. It is the intrinsic 'inactive' tendency of SMCA that contributes to the different rates of graft disease between SV and ITA after CABG.
Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Yongxin
Y
Sun
Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Le
L
Kang
Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Jun
J
Li
Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Huan
H
Liu
Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Yulin
Y
Wang
Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. wang.chunsheng@zs-hospital.sh.cn.
Chunsheng
C
Wang
Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China. zou.yunzeng@zs-hospital.sh.cn.
Yunzeng
Y
Zou
D049109:Cell Proliferation / Q000187:drug effects; D003710:Demography; D003920:Diabetes Mellitus / Q000378:metabolism / Q000473:pathology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D017127:Glycation End Products, Advanced / Q000633:toxicity*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*; D012501:Saphenous Vein / Q000473:pathology*; D013895:Thoracic Arteries / Q000473:pathology*
D017127:Glycation End Products, Advanced; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
RAGE; advanced glycation end products; mitogen activated protein kinase signalling pathway; saphenous vein; smooth muscle cells