Effect of CC Chemokine Receptor 2 CCR2 Blockade on Serum C-reactive Protein in Individuals at Atherosclerotic Risk and With a Single Nucleotide Polymorphism of the Monocyte Chemoattractant protein-1 Promoter Region

Am J Cardiol. 2011 Mar 15;107(6):906-11. doi: 10.1016/j.amjcard.2010.11.005. Epub 2011 Jan 19.

Abstract

CC chemokine receptor 2 (CCR2), expressed on the surface of circulating monocytes, and its ligand monocyte chemoattractant protein-1 (MCP-1; also known as CC-chemokine ligand 2) are present in atherosclerotic plaques and may have important roles in endothelial monocyte recruitment and activation. MLN1202 is a highly specific humanized monoclonal antibody that interacts with CCR2 and inhibits MCP-1 binding. The aim of this randomized, double-blind, placebo-controlled study was to measure reductions in circulating levels of high-sensitivity C-reactive protein, an established biomarker of inflammation associated with coronary artery disease, on MLN1202 treatment in patients at risk for atherosclerotic cardiovascular disease (≥2 risk factors for atherosclerotic cardiovascular disease and circulating high-sensitivity C-reactive protein >3 mg/L). Additionally, patients were genotyped for the 2518 A→G polymorphism in the promoter of the MCP-1 gene to investigate the correlation between this polymorphism and reduced C-reactive protein levels with MLN1202 treatment. Patients who received MLN1202 exhibited significant decreases in high-sensitivity C-reactive protein levels, beginning at 4 weeks and continuing through 12 weeks after dosing. Patients with A/G or G/G genotypes in the MCP-1 promoter had significantly greater reductions in high-sensitivity C-reactive protein levels than patients with the wild-type A/A genotype. In conclusion, MLN1202 treatment was well tolerated in this patient population and resulted in significant reductions in high-sensitivity C-reactive protein levels.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Humanized
  • Biomarkers / metabolism
  • C-Reactive Protein / metabolism*
  • Chemokine CCL2 / genetics*
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / genetics*
  • Double-Blind Method
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Placebos
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic
  • Receptors, CCR2 / antagonists & inhibitors*
  • Risk Factors
  • Statistics, Nonparametric

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • Chemokine CCL2
  • Placebos
  • Receptors, CCR2
  • plozalizumab
  • C-Reactive Protein