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J Cell Biochem. 2012 Mar;113(3):857-67. doi: 10.1002/jcb.23415.

C-reactive protein promotes adhesion of monocytes to endothelial cells via NADPH oxidase-mediated oxidative stress.

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1
The Key Laboratory of Geriatrics, Beijing Hospital &Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, PR China.

Abstract

Enhanced monocyte adhesion to endothelial cells is an early event in atherogenesis. It has been shown that C-reactive protein (CRP) plays a key role in atherogenesis. Here, we investigated the effects of CRP on monocyte-endothelial cell adhesion and tested the hypothesis that NADPH oxidase (NOX)-mediated oxidative stress might play a key role in CRP-induced monocyte-endothelial cell adhesion. Firstly, 36 patients with carotid intima-media thickness (IMT) incrassation and 34 controls were enrolled in this study. The levels of glucose, lipids, CRP, monocyte chemotractant protein (MCP-1), malondialdehyde (MDA), and protein carbonylation were analyzed. The results showed that carotid IMT was associated with abnormal lipid metabolism, including elevated CRP, triglycerides (TG) (P < 0.01) and decreased high density lipoprotein (HDL) level (P < 0.05). The levels of CRP and MCP-1 in patients with carotid IMT incrassation were increased compared with the controls (P < 0.01). Moreover, patients with carotid IMT incrassation displayed enhanced MDA and protein carbonylation levels (P < 0.01), accompanied by activation and up-regulation of NOX in monocytes (P < 0.05) compared with the controls. The monocytes isolated from five healthy donors were used for in vitro experiments. Reactive oxygen species (ROS) production and NOX expression in monocytes were examined. The results also indicated that CRP could promote the adhesion of monocyte-endothelial cell by up-regulation of MCP-1 expression (P < 0.05). Importantly, NFκ B and p38 MAPK signaling pathways, which were activated by NOX-derived ROS, were involved in CRP-induced monocyte-endothelial cell adhesion and up-regulation of MCP-1 expression. These data suggested that CRP could promote the adhesion of monocytes to endothelial cells via NOX-mediated oxidative stress. J. Cell. Biochem. 113: 857-867, 2012. © 2011 Wiley Periodicals, Inc.

PMID:
22020763
DOI:
10.1002/jcb.23415
[Indexed for MEDLINE]
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