PMID- 21247529
OWN - NLM
STAT- MEDLINE
DCOM- 20110603
LR  - 20191210
IS  - 1879-1913 (Electronic)
IS  - 0002-9149 (Linking)
VI  - 107
IP  - 6
DP  - 2011 Mar 15
TI  - 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.
PG  - 906-11
LID - 10.1016/j.amjcard.2010.11.005 [doi]
AB  - 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.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Gilbert, Jim
AU  - Gilbert J
AD  - Archemix Corporation, Cambridge, MA, USA. jgilbert@archemix.com
FAU - Lekstrom-Himes, Julie
AU  - Lekstrom-Himes J
FAU - Donaldson, Debra
AU  - Donaldson D
FAU - Lee, Yih
AU  - Lee Y
FAU - Hu, Mingxiu
AU  - Hu M
FAU - Xu, Jing
AU  - Xu J
FAU - Wyant, Tim
AU  - Wyant T
FAU - Davidson, Michael
AU  - Davidson M
CN  - MLN1202 Study Group
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20110119
PL  - United States
TA  - Am J Cardiol
JT  - The American journal of cardiology
JID - 0207277
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Biomarkers)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Placebos)
RN  - 0 (Receptors, CCR2)
RN  - 4XG66BMN0D (plozalizumab)
RN  - 9007-41-4 (C-Reactive Protein)
SB  - IM
MH  - Antibodies, Monoclonal/*pharmacology
MH  - Antibodies, Monoclonal, Humanized
MH  - Biomarkers/metabolism
MH  - C-Reactive Protein/*metabolism
MH  - Chemokine CCL2/*genetics
MH  - Coronary Artery Disease/*blood/*genetics
MH  - Double-Blind Method
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Placebos
MH  - *Polymorphism, Single Nucleotide
MH  - Promoter Regions, Genetic
MH  - Receptors, CCR2/*antagonists & inhibitors
MH  - Risk Factors
MH  - Statistics, Nonparametric
FIR - Conner, Gordon
IR  - Conner G
FIR - Poque, Bryan
IR  - Poque B
FIR - Ellison, Travis
IR  - Ellison T
FIR - Pierson, Monica
IR  - Pierson M
FIR - Zavoral, James
IR  - Zavoral J
FIR - Halpern, Stephen
IR  - Halpern S
FIR - Severance, Randall
IR  - Severance R
FIR - Fiske, Darrell
IR  - Fiske D
EDAT- 2011/01/21 06:00
MHDA- 2011/06/04 06:00
CRDT- 2011/01/21 06:00
PHST- 2010/07/09 00:00 [received]
PHST- 2010/11/03 00:00 [revised]
PHST- 2010/11/03 00:00 [accepted]
PHST- 2011/01/21 06:00 [entrez]
PHST- 2011/01/21 06:00 [pubmed]
PHST- 2011/06/04 06:00 [medline]
AID - S0002-9149(10)02414-8 [pii]
AID - 10.1016/j.amjcard.2010.11.005 [doi]
PST - ppublish
SO  - Am J Cardiol. 2011 Mar 15;107(6):906-11. doi: 10.1016/j.amjcard.2010.11.005. Epub 
      2011 Jan 19.