Advanced oxidation protein products induce monocyte chemoattractant protein-1 expression via p38 mitogen-activated protein kinase activation in rat vascular smooth muscle cells.
- Author:
Kan-fu PENG
1
;
Xiong-fei WU
;
Hong-wen ZHAO
;
Yan SUN
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Atherosclerosis; etiology; Cardiovascular Diseases; etiology; Cells, Cultured; Chemokine CCL2; genetics; Enzyme Activation; Imidazoles; pharmacology; Kidney Failure, Chronic; complications; Male; Muscle, Smooth, Vascular; cytology; metabolism; Myocytes, Smooth Muscle; metabolism; Oxidation-Reduction; Proteins; metabolism; Pyridines; pharmacology; RNA, Messenger; analysis; Rats; Rats, Sprague-Dawley; Uremia; metabolism; p38 Mitogen-Activated Protein Kinases; physiology
- From: Chinese Medical Journal 2006;119(13):1088-1093
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDAdvanced oxidation protein products (AOPPs) are new uremic toxins reported by Witko-Sarsat in 1996, which are associated with the pathogenesis of atherosclerosis. However, the mechanisms by which AOPPs enhance atherosclerosis have not been fully understood. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine which stimulates migration of monocytes and plays a critical role in the development of atherosclerosis. In this study, we investigated the effect of AOPPs on MCP-1 expression in cultured vascular smooth muscle cells (VSMCs).
METHODSVSMCs were cultured and then co-incubated with AOPP (200 micromol/L, 400 micromol/L) for different times with or without pretreatment with specific p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580. RT-PCR and Western blott were used to detect MCP-1 mRNA and protein expression at different time points after AOPP stimulation in rat smooth muscle cells. Western blot was used to detect the expression of phosphorylated p38 MAPK.
RESULTSTreatment of VSMC with AOPPs resulted in a significant increase of the expression of MCP-1 mRNA and protein in time- and dose-dependent manner, and could activated p38 MAPK. Pretreatment of VSMCs with SB203580 resulted in a dose-dependent inhibition of AOPPs-induced MCP-1 mRNA and protein expression.
CONCLUSIONSAOPPs can stimulate MCP-1 expression via p38 MAPK in VSMCs. This suggests that AOPPs might contribute to the formation of atherosclerosis through this proinflammatory effect.
