Raised MCP-4 levels in symptomatic carotid atherosclerosis: an inflammatory link between platelet and monocyte activation.

Research Institute for Internal Medicine, University of Oslo, Oslo, Norway.

Cardiovascular research 2010 May 1

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Several studies suggest a pro-atherogenic role for the CC chemokine receptor 2 (CCR2), thought to reflect interaction with monocyte chemoattractant protein (MCP)-1. Based on its ability to attract leucocytes into inflamed tissue, we hypothesized a pro-atherogenic role for MCP-4, another CCR2 ligand. Our main findings were: (i) patients with symptomatic carotid stenosis (n = 29), but not those with asymptomatic plaques (n = 31), had significantly raised plasma levels of MCP-4 compared with healthy controls (n = 20); (ii) in vitro, releasate from activated platelets markedly increased the expression of MCP-4 and CCR2 in THP-1 monocytes, and enhanced the MCP-4-mediated effect on interleukin-8 secretion in these cells, involving the platelet-derived chemokine RANTES; (iii) while MCP-1 had no effect on the release of RANTES and interferon-inducible protein of 10 kDa in tumour necrosis factor alpha-pre-activated THP-1 monocytes, MCP-4 profoundly enhanced the release of these pro-atherogenic chemokines; and (iv) the data indicate an inflammatory interaction between RANTES and MCP-4, involving CCR2, and mRNA levels of these mediators were markedly up-regulated within symptomatic atherosclerotic carotid plaque (n = 81). Our findings suggest that the pro-atherogenic effects of CCR2 may not be restricted to interaction with MCP-1, but could also involve activation by MCP-4, being an inflammatory link between platelet and monocyte activation.

Citation

Unni M Breland, Annika E Michelsen, Mona Skjelland, Lasse Folkersen, Kirsten Krohg-Sørensen, David Russell, Thor Ueland, Arne Yndestad, Gabrielle Paulsson-Berne, Jan K Damås, Erik Oie, Gøran K Hansson, Bente Halvorsen, Pål Aukrust. Raised MCP-4 levels in symptomatic carotid atherosclerosis: an inflammatory link between platelet and monocyte activation. Cardiovascular research. 2010 May 1;86(2):265-73