Journal
ATHEROSCLEROSIS
Volume 213, Issue 2, Pages 415-421Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2010.09.033
Keywords
Atherosclerosis; Monocytes; Cyclophilin A; EMMPRIN (extracellular matrix metalloproteinase inducer); Matrix metalloproteinase-9(MMP-9)
Funding
- National Natural Science Foundation of China [81000114, 30670880, 30600242]
- Shanghai Municipal Education Commission [jdy07038]
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Excessive reactive oxygen species (ROS) is a critical driver of vascular inflammation in atherosclerosis. Cyclophilin A (CyPA) is the main ROS-induced factor that enhances the inflammatory activity of monocytes/macrophages in atherosclerotic plaque. However, the means by which CyPA interacts with monocytes/macrophages is unclear. Through Chemotaxis assay and ELISA test, we found CyPA strongly induced migration of monocytes and the expression of mmp-9, IL-6 and TNF-alpha. By Western blot, it demonstrated that CyPA activated NF-kappaB by ERK1/2 pathway. When blocking extracellular matrix metalloproteinase inducer (EMMPRIN) in monocytes, most of the CyPA effects including chemoattractant migration, activation of MAPK/NF-kappaB and cytokines releasing were significantly inhibited. Finally, CyPA simulation had no effect on EMMPRIN expression in monocytes. The current study shows that CyPA-EMMPRIN interaction is one of the key pro-inflammatory signaling pathways in monocytes, perhaps especially in response to ROS stimulation. This could be a potential target for atherosclerosis therapy. Crown Copyright (C) 2010 Published by Elsevier Ireland Ltd. All rights reserved.
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