CCR2-/- knockout mice revascularize normally in response to severe hindlimb ischemia

¹Pacific Vascular Research Laboratory, Department of Surgery, Division of Vascular Surgery, University of California, San Francisco 94143-0222, USA.

|October 9, 2004

Summary

Monocyte chemoattractant protein-1 (MCP-1) signaling via its receptor CC-chemokine receptor 2 (CCR2) is not essential for collateral artery development after hindlimb ischemia. Alternative pathways, like ICAM-1, may compensate for CCR2 deficiency in promoting arteriogenesis.

Area of Science:

Cardiovascular Biology
Immunology
Vascular Biology

Background:

Monocyte chemoattractant protein-1 (MCP-1) is implicated in ischemia-induced arteriogenesis by recruiting monocytes and macrophages.
CC-chemokine receptor 2 (CCR2) is the primary receptor for MCP-1.
The role of CCR2 in mediating MCP-1's effects on arteriogenesis requires further investigation.

Purpose of the Study:

To investigate whether MCP-1-mediated arteriogenesis in response to hindlimb ischemia is dependent on its receptor, CCR2.
To assess the impact of CCR2 deficiency on limb blood flow recovery, collateral artery development, and inflammatory cell recruitment.

Main Methods:

Hindlimb ischemia was surgically induced in mice lacking CCR2 (CCR2 -/-) and wild-type controls.
Limb blood flow recovery was quantified using laser Doppler perfusion imaging.
Collateral artery development was assessed via angiography.
Monocyte and macrophage infiltration into ischemic tissues was evaluated by histological analysis.
Gene expression of MCP-1 and Intercellular Adhesion Molecule-1 (ICAM-1) was measured using mRNA analysis.

Main Results:

CCR2 -/- mice exhibited equivalent hindlimb blood flow recovery compared to wild-type mice.
Collateral artery development was not significantly different between CCR2 -/- and wild-type mice.
While monocyte and macrophage recruitment to the ischemic calf was reduced by 44% in CCR2 -/- mice, recruitment to the thigh remained similar.
Intercellular adhesion molecule-1 (ICAM-1) and MCP-1 mRNA levels were significantly upregulated in the thigh muscle of CCR2 -/- mice.

Conclusions:

MCP-1 signaling through CCR2 is not essential for arteriogenesis and blood flow recovery following severe hindlimb ischemia.
Monocyte and macrophage recruitment to the ischemic thigh occurs normally in CCR2 -/- mice, suggesting alternative compensatory mechanisms.
Upregulation of ICAM-1 may play a role in substituting for CCR2-mediated signaling, enabling normal arteriogenesis in CCR2-deficient mice.

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CCR2-/- knockout mice revascularize normally in response to severe hindlimb ischemia

Area of Science:

Background:

Purpose of the Study:

Main Methods:

Main Results:

Conclusions:

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