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

Cardiovasc Res. 2010 May 1;86(2):265-73. doi: 10.1093/cvr/cvq044. Epub 2010 Feb 5.

Abstract

Aims: 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.

Methods and results: 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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carotid Stenosis / blood
  • Carotid Stenosis / complications
  • Carotid Stenosis / immunology*
  • Case-Control Studies
  • Cell Line
  • Chemokine CCL5 / metabolism
  • Disease Progression
  • Female
  • Humans
  • Inflammation / blood
  • Inflammation / complications
  • Inflammation / immunology*
  • Inflammation Mediators / blood*
  • Interleukin-8 / metabolism
  • Male
  • Middle Aged
  • Monocyte Chemoattractant Proteins / blood*
  • Monocytes / immunology*
  • Platelet Activation*
  • Receptors, CCR2 / metabolism
  • Severity of Illness Index
  • Up-Regulation

Substances

  • CCL13 protein, human
  • CCL5 protein, human
  • CCR2 protein, human
  • CXCL8 protein, human
  • Chemokine CCL5
  • Inflammation Mediators
  • Interleukin-8
  • Monocyte Chemoattractant Proteins
  • Receptors, CCR2