PMID- 19052854
OWN - NLM
STAT- MEDLINE
DCOM- 20090511
LR  - 20171116
IS  - 1573-7241 (Electronic)
IS  - 0920-3206 (Linking)
VI  - 23
IP  - 2
DP  - 2009 Apr
TI  - A CCR2/CCR5 antagonist attenuates an increase in angiotensin II-induced CD11b+ 
      monocytes from atherogenic ApoE-/- mice.
PG  - 113-20
LID - 10.1007/s10557-008-6157-0 [doi]
AB  - OBJECTIVE: Monocyte infiltration into the vessel wall, a process primarily 
      mediated by the interaction between monocyte chemoattractant protein-1 (MCP-1) 
      and its receptor, CCR2, is a key step in atherogenesis. Angiotensin II (Ang II) 
      enhances this monocyte infiltration by increasing the endothelial binding 
      integrin, CD11b. However, the modulation of the Ang II-induced CD11b expression 
      in monocytes in not clear. The aim of this study was to determine if MCP-1/MCP-2 
      receptor (CCR2) interaction regulates monocyte CD11b expression after 7 days of 
      Ang II infusion. METHODS AND RESULTS: In ApoE(-/-) mice continuous subcutaneous 
      infusion of Ang II (0.75 mg/kg/day) for 7 days significantly increased CD11b 
      expression in circulating monocytes as measured by flow cytometry. CD11b 
      expression in ApoE(-/-) was increased from 135 +/- 9 to 176 +/- 12 mean 
      fluorescent intensity (MFI), control and Ang II-treated, respectively while in 
      C57B/J wildtype mice CD11b increased from 128 +/- 13 to 174 +/- 8 MFI, control 
      and Ang II-treated, respectively. Interestingly, co-infusion of either MCP-1 
      neutralizing antibody (25 microg/kg/day) or a CCR2 antagonist (500 microg/kg/day) 
      with Ang II for 7 days effectively inhibited monocyte CD11b expression and this 
      inhibition was accompanied by a down-regulated vascular infiltration of Mac-2 
      positive monocyte-derived macrophages. CONCLUSION: Our data in the atherogenic 
      ApoE(-/-) mouse demonstrates that the Ang II induced increase in both monocytic 
      CD11b integrin expression and monocyte vascular infiltration occurs early in 
      atherogenesis. These Ang II-induced monocytic changes are in part regulated 
      through the MCP-1/CCR2 interaction.
FAU - Major, Terry C
AU  - Major TC
AD  - Cardiovascular and Atherosclerosis Biology, Pfizer Global Research and 
      Development, Ann Arbor, MI, USA. tcmajor@umich.edu
FAU - Olszewski, Bronia
AU  - Olszewski B
FAU - Rosebury-Smith, Wendy S
AU  - Rosebury-Smith WS
LA  - eng
PT  - Journal Article
DEP - 20081204
PL  - United States
TA  - Cardiovasc Drugs Ther
JT  - Cardiovascular drugs and therapy
JID - 8712220
RN  - 0 (Apolipoproteins E)
RN  - 0 (CCR5 Receptor Antagonists)
RN  - 0 (CD11b Antigen)
RN  - 0 (Receptors, CCR2)
RN  - 11128-99-7 (Angiotensin II)
SB  - IM
MH  - Angiotensin II/*administration & dosage
MH  - Animals
MH  - Apolipoproteins E/genetics
MH  - Atherosclerosis/*metabolism/pathology
MH  - CCR5 Receptor Antagonists
MH  - CD11b Antigen/genetics/*metabolism
MH  - Flow Cytometry
MH  - Gene Expression Regulation
MH  - Humans
MH  - Macrophages/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Monocytes/metabolism
MH  - Rats
MH  - Receptors, CCR2/antagonists & inhibitors/*metabolism
EDAT- 2008/12/05 09:00
MHDA- 2009/05/12 09:00
CRDT- 2008/12/05 09:00
PHST- 2008/09/13 00:00 [received]
PHST- 2008/11/17 00:00 [accepted]
PHST- 2008/12/05 09:00 [pubmed]
PHST- 2009/05/12 09:00 [medline]
PHST- 2008/12/05 09:00 [entrez]
AID - 10.1007/s10557-008-6157-0 [doi]
PST - ppublish
SO  - Cardiovasc Drugs Ther. 2009 Apr;23(2):113-20. doi: 10.1007/s10557-008-6157-0. 
      Epub 2008 Dec 4.