PMID- 12574150
OWN - NLM
STAT- MEDLINE
DCOM- 20030214
LR  - 20190706
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 92
IP  - 2
DP  - 2003 Feb 7
TI  - Local monocyte chemoattractant protein-1 therapy increases collateral artery 
      formation in apolipoprotein E-deficient mice but induces systemic monocytic CD11b 
      expression, neointimal formation, and plaque progression.
PG  - 218-25
AB  - Monocyte chemoattractant protein-1 (MCP-1) stimulates the formation of a 
      collateral circulation on arterial occlusion. The present study served to 
      determine whether these proarteriogenic properties of MCP-1 are preserved in 
      hyperlipidemic apolipoprotein E-deficient (apoE-/-) mice and whether it affects 
      the systemic development of atherosclerosis. A total of 78 apoE-/- mice were 
      treated with local infusion of low-dose MCP-1 (1 microg/kg per week), high-dose 
      MCP-1 (10 microg/kg per week), or PBS as a control after unilateral ligation of 
      the femoral artery. Collateral hindlimb flow, measured with fluorescent 
      microspheres, significantly increased on a 1-week high-dose MCP-1 treatment (PBS 
      22.6+/-7.2%, MCP-1 31.3+/-10.3%; P<0.05). These effects were still present 2 
      months after the treatment (PBS 44.3+/-4.6%, MCP-1 56.5+/-10.4%; P<0.001). The 
      increase in collateral flow was accompanied by an increase in the number of 
      perivascular monocytes/macrophages on MCP-1 treatment. However, systemic CD11b 
      expression by monocytes also increased, as did monocyte adhesion at the aortic 
      endothelium and neointimal formation (intima/media ratio, 0.097+/-0.011 [PBS] 
      versus 0.257+/-0.022 [MCP-1]; P<0.0001). Moreover, Sudan IV staining revealed an 
      increase in aortic atherosclerotic plaque surface (24.3+/-5.2% [PBS] versus 
      38.2+/-9.5% [MCP-1]; P<0.01). Finally, a significant decrease in the percentage 
      of smooth muscle cells was found in plaques (15.0+/-5.2% [PBS] versus 5.8+/-2.3% 
      [MCP-1]; P<0.001). In conclusion, local infusion of MCP-1 significantly increases 
      collateral flow on femoral artery ligation in apoE-/- mice up to 2 months after 
      the treatment. However, the local treatment did not preclude systemic effects on 
      atherogenesis, leading to increased atherosclerotic plaque formation and changes 
      in cellular content of plaques.
FAU - van Royen, N
AU  - van Royen N
AD  - Department of Cardiology, University of Amsterdam, Amsterdam, The Netherlands. 
      n.vanroyen@amc.uva.nl
FAU - Hoefer, I
AU  - Hoefer I
FAU - Bottinger, M
AU  - Bottinger M
FAU - Hua, J
AU  - Hua J
FAU - Grundmann, S
AU  - Grundmann S
FAU - Voskuil, M
AU  - Voskuil M
FAU - Bode, C
AU  - Bode C
FAU - Schaper, W
AU  - Schaper W
FAU - Buschmann, I
AU  - Buschmann I
FAU - Piek, J J
AU  - Piek JJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Apolipoproteins E)
RN  - 0 (CD11b Antigen)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Lipids)
SB  - IM
MH  - Animals
MH  - Apolipoproteins E/deficiency/genetics
MH  - Arteries/*drug effects/pathology
MH  - Arteriosclerosis/pathology
MH  - CD11b Antigen/*biosynthesis
MH  - Chemokine CCL2/adverse effects/*pharmacology
MH  - Collateral Circulation/*drug effects
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Dose-Response Relationship, Drug
MH  - Femoral Artery/drug effects/pathology
MH  - Flow Cytometry
MH  - Immunohistochemistry
MH  - Lipids/blood
MH  - Macrophages/drug effects/pathology
MH  - Mice
MH  - Mice, Knockout
MH  - Monocytes/drug effects/*metabolism/pathology
MH  - Regional Blood Flow/drug effects
MH  - Tunica Intima/*drug effects/pathology
EDAT- 2003/02/08 04:00
MHDA- 2003/02/15 04:00
CRDT- 2003/02/08 04:00
PHST- 2003/02/08 04:00 [pubmed]
PHST- 2003/02/15 04:00 [medline]
PHST- 2003/02/08 04:00 [entrez]
AID - 10.1161/01.res.0000052313.23087.3f [doi]
PST - ppublish
SO  - Circ Res. 2003 Feb 7;92(2):218-25. doi: 10.1161/01.res.0000052313.23087.3f.