PMID- 12618265
OWN - NLM
STAT- MEDLINE
DCOM- 20030723
LR  - 20190718
IS  - 0021-9150 (Print)
IS  - 0021-9150 (Linking)
VI  - 167
IP  - 1
DP  - 2003 Mar
TI  - CCR5 deficiency is not protective in the early stages of atherogenesis in apoE 
      knockout mice.
PG  - 25-32
AB  - The accumulation of macrophages and T lymphocytes in vessel walls is a hallmark 
      of atherogenesis. It has recently been demonstrated in mouse models of 
      atherosclerosis that full disease potential is dependent on several regulators of 
      leukocyte trafficking, including the chemokine monocyte chemotactic protein 1 
      (MCP-1) and the chemokine receptors CCR2 and CXCR2. A possible role for the 
      chemokine receptor CCR5 in atherogenesis has been suggested by CCR5 expression on 
      macrophages, T cells, coronary endothelial cells and aortic smooth muscle cells 
      and by the presence of CCR5 ligands in atherosclerotic plaques. Moreover, 
      individuals who are naturally deficient in CCR5 were reported to be at reduced 
      risk for severe coronary artery disease (CAD) and early myocardial infarction 
      (MI). To investigate whether CCR5 is pro-atherogenic in mice, we generated 
      CCR5-deficient mice and crossed them with atherosclerosis-prone apoE-deficient 
      mice. Although CCR5-deficient mice exhibit defects in induced macrophage 
      trafficking, mean atherosclerotic lesion area did not differ significantly 
      between apoE-deficient mice and apoE/CCR5-deficient mice after 16 weeks on a diet 
      of normal chow. Ribonuclease protection assays (RPA) on RNA isolated from plaques 
      from both apoE-deficient and apoE/CCR5-deficient animals showed strong signals 
      for the macrophage marker F4/80 but no evidence for expression of prominent 
      markers of T and B lymphocytes. These results indicate that the early stages of 
      plaque formation in this model of lipid-mediated atherogenesis do not depend on 
      CCR5.
FAU - Kuziel, William A
AU  - Kuziel WA
AD  - Section of Molecular Genetics and Microbiology and Institute of Cellular and 
      Molecular Biology, The University of Texas at Austin, 1 University Station A5000, 
      Austin 78712, USA. wakuziel@mail.utexas.edu
FAU - Dawson, Tracey C
AU  - Dawson TC
FAU - Quinones, Marlon
AU  - Quinones M
FAU - Garavito, Edgar
AU  - Garavito E
FAU - Chenaux, George
AU  - Chenaux G
FAU - Ahuja, Seema S
AU  - Ahuja SS
FAU - Reddick, Robert L
AU  - Reddick RL
FAU - Maeda, Nobuyo
AU  - Maeda N
LA  - eng
GR  - HL42630/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (Apolipoproteins E)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Receptors, CCR5)
RN  - 0 (Receptors, Chemokine)
RN  - 63231-63-0 (RNA)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Apolipoproteins E/*metabolism
MH  - Arteriosclerosis/*etiology/*prevention & control
MH  - Blotting, Northern
MH  - Chemokine CCL2/genetics/*physiology
MH  - Lipoproteins, LDL/analysis
MH  - Macrophages/*physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Probability
MH  - RNA/analysis
MH  - Receptors, CCR5/*deficiency
MH  - Receptors, Chemokine/metabolism
MH  - Sensitivity and Specificity
MH  - Severity of Illness Index
EDAT- 2003/03/06 04:00
MHDA- 2003/07/24 05:00
CRDT- 2003/03/06 04:00
PHST- 2003/03/06 04:00 [pubmed]
PHST- 2003/07/24 05:00 [medline]
PHST- 2003/03/06 04:00 [entrez]
AID - S0021-9150(02)00382-9 [pii]
AID - 10.1016/s0021-9150(02)00382-9 [doi]
PST - ppublish
SO  - Atherosclerosis. 2003 Mar;167(1):25-32. doi: 10.1016/s0021-9150(02)00382-9.