PMID- 9732872
OWN - NLM
STAT- MEDLINE
DCOM- 19990211
LR  - 20220408
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 394
IP  - 6696
DP  - 1998 Aug 27
TI  - Decreased lesion formation in CCR2-/- mice reveals a role for chemokines in the 
      initiation of atherosclerosis.
PG  - 894-7
AB  - Chemokines are proinflammatory cytokines that function in leukocyte 
      chemoattraction and activation and have recently been shown to block the HIV-1 
      infection of target cells through interactions with chemokine receptors. In 
      addition to their function in viral disease, chemokines have been implicated in 
      the pathogenesis of atherosclerosis. Expression of the CC chemokine monocyte 
      chemoattractant protein-1 (MCP-1) is upregulated in human atherosclerotic 
      plaques, in arteries of primates on a hypercholesterolaemic diet; and in vascular 
      endothelial and smooth muscle cells exposed to minimally modified lipids. To 
      determine whether MCP-1 is causally related to the development of 
      atherosclerosis, we generated mice that lack CCR2, the receptor for MCP-1 (ref. 
      7), and crossed them with apolipoprotein (apo) E-null mice which develop severe 
      atherosclerosis. Here we show that the selective absence of CCR2 decreases lesion 
      formation markedly in apoE-/- mice but has no effect on plasma lipid or 
      lipoprotein concentrations. These data reveal a role for MCP-1 in the development 
      of early atherosclerotic lesions and suggest that upregulation of this chemokine 
      by minimally oxidized lipids is an important link between hyperlipidaemia and 
      fatty streak formation.
FAU - Boring, L
AU  - Boring L
AD  - Gladstone Institute of Cardiovascular Disease, San Francisco, California 94141, 
      USA.
FAU - Gosling, J
AU  - Gosling J
FAU - Cleary, M
AU  - Cleary M
FAU - Charo, I F
AU  - Charo IF
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Apolipoproteins E)
RN  - 0 (CCR2 protein, human)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Lipoproteins)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Receptors, Cytokine)
RN  - 0 (Triglycerides)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Animals
MH  - Aorta/pathology
MH  - Apolipoproteins E/physiology
MH  - Arteriosclerosis/blood/*etiology/pathology
MH  - Chemokine CCL2/*physiology
MH  - Cholesterol/blood
MH  - Diet, Atherogenic
MH  - Lipoproteins/blood
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myocardium/pathology
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/physiology
MH  - Receptors, Cytokine/genetics/*physiology
MH  - Triglycerides/blood
EDAT- 1998/09/11 02:02
MHDA- 2001/03/23 10:01
CRDT- 1998/09/11 02:02
PHST- 1998/09/11 02:02 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1998/09/11 02:02 [entrez]
AID - 10.1038/29788 [doi]
PST - ppublish
SO  - Nature. 1998 Aug 27;394(6696):894-7. doi: 10.1038/29788.