PMID- 15472609
OWN - NLM
STAT- MEDLINE
DCOM- 20041116
LR  - 20121003
IS  - 0741-5214 (Print)
IS  - 0741-5214 (Linking)
VI  - 40
IP  - 4
DP  - 2004 Oct
TI  - CCR2-/- knockout mice revascularize normally in response to severe hindlimb 
      ischemia.
PG  - 786-95
AB  - OBJECTIVE: Monocyte chemoattractant protein-1 (MCP-1) is reported to stimulate 
      ischemia-induced arteriogenesis (collateral artery development) by recruiting 
      monocytes and macrophages into areas of active arteriogenesis. To determine 
      whether the MCP-1-mediated response occurs through its receptor, CC-chemokine 
      receptor 2 (CCR2), we induced hindlimb ischemia in mice lacking the receptor for 
      MCP-1 (CCR2 -/- ) and measured limb blood flow recovery, collateral artery 
      development, and monocyte and macrophage recruitment. METHODS AND RESULTS: 
      Hindlimb ischemia was induced by excising the left femoral artery in CCR2 -/- and 
      wild-type mice. Hindlimb blood flow recovery, as measured using laser Doppler 
      perfusion imaging, was equivalent in both groups ( P = .78 for foot and P = 0.38 
      for calf). Collateral artery development, as measured by angiography at 
      postoperative day 14 and 31, likewise did not differ between the 2 groups ( P = 
      .46 and P = .67). Counts of monocytes and macrophages in calf and thigh muscle 
      sections of mice sacrificed on postoperative day 7 revealed that although CCR2 
      -/- mice recruited 44% fewer monocytes and macrophages to areas of ischemia in 
      the calf, they recruited similar numbers of monocytes and macrophages to areas of 
      active arteriogenesis in the thigh. Intercellular adhesion molecule-1 and MCP-1 
      mRNA levels were higher in the thigh muscle of CCR2 -/- mice than in wild-type 
      mice (5.5-fold and 42.3-fold induction operated to unoperated vs 2.6-fold and 
      6.1-fold induction operated to unoperated, respectively). CONCLUSIONS: Blood flow 
      recovery, arteriogenesis, and monocyte and macrophage recruitment to the thigh 
      was normal in CCR2 -/- mice. However, monocyte and macrophage recruitment to the 
      ischemic calf was diminished in CCR2 -/- mice. Our results show that MCP-1 
      signaling through CCR2 is not required for physiologic arteriogenesis in response 
      to severe hindlimb ischemia. ICAM-1 upregulation may substitute for MCP-1 
      signaling through CCR2 in order to allow normal arteriogenesis in CCR2 -/- mice.
FAU - Tang, Gale
AU  - Tang G
AD  - Pacific Vascular Research Laboratory, Department of Surgery, Division of Vascular 
      Surgery, University of California, San Francisco 94143-0222, USA.
FAU - Charo, David N
AU  - Charo DN
FAU - Wang, Rong
AU  - Wang R
FAU - Charo, Israel F
AU  - Charo IF
FAU - Messina, Louis
AU  - Messina L
LA  - eng
GR  - HL52773/HL/NHLBI NIH HHS/United States
GR  - HL63894/HL/NHLBI NIH HHS/United States
GR  - HL68402/HL/NHLBI NIH HHS/United States
GR  - HL75353/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  - United States
TA  - J Vasc Surg
JT  - Journal of vascular surgery
JID - 8407742
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
SB  - IM
MH  - Animals
MH  - Blood Flow Velocity/physiology
MH  - Chemokine CCL2/*physiology
MH  - Chemotaxis/physiology
MH  - Female
MH  - Hindlimb/*blood supply
MH  - Ischemia/*physiopathology
MH  - Macrophages/physiology
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Models, Animal
MH  - Monocytes/physiology
MH  - Neovascularization, Physiologic/*physiology
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/*physiology
EDAT- 2004/10/09 09:00
MHDA- 2004/11/17 09:00
CRDT- 2004/10/09 09:00
PHST- 2004/10/09 09:00 [pubmed]
PHST- 2004/11/17 09:00 [medline]
PHST- 2004/10/09 09:00 [entrez]
AID - S0741521404009292 [pii]
AID - 10.1016/j.jvs.2004.07.012 [doi]
PST - ppublish
SO  - J Vasc Surg. 2004 Oct;40(4):786-95. doi: 10.1016/j.jvs.2004.07.012.