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J Am Coll Cardiol. 2004 Aug 4;44(3):661-6.

Roles of endogenous monocyte chemoattractant protein-1 in ischemia-induced neovascularization.

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1
Third Department of Internal Medicine and Cardiovascular Research Institute, Kurume University, Kurume, Japan.

Abstract

OBJECTIVES:

We sought to investigate the role of endogenous monocyte chemoattractant protein (MCP)-1 in ischemia-induced neovascularization.

BACKGROUND:

Roles of inflammatory changes including macrophage infiltration are suggested in ischemic neovascularization.

METHODS:

Unilateral hindlimb ischemia was induced by excising surgically the entire femoral artery and vein in mice. Immediately after operation, plasmid deoxyribonucleic acid encoding a dominant negative mutant of MCP-1 (7ND) or the empty plasmid (mock) was injected into the ipsilateral thigh adductor muscle.

RESULTS:

In mock-treated mice, MCP-1 was upregulated transiently in ischemic hindlimb peaking at day 3. Serial laser Doppler blood flow (LDBF) analysis showed an abrupt decrease in blood flow, followed by a recovery to the near-normal levels in mock-treated mice; 7ND treatment had no effects on the initial decrease in LDBF but deteriorated the recovery. At day 3, macrophage infiltration and inductions of tumor necrosis factor (TNF)-alpha and vascular endothelial growth factor (VEGF) were prominent in the ischemic adductor muscle in mock-treated mice; 7ND treatment significantly reduced macrophage infiltration and suppressed TNF-alpha and VEGF inductions in response to ischemia. At day 21, postmortem angiography and anti-CD31 immunohistostaining revealed well-developed collateral vessels and capillary formation, respectively, in the ischemic muscle of mock-treated mice; 7ND overexpression remarkably suppressed the collateral vessel formation and capillary formation.

CONCLUSIONS:

Endogenous MCP-1 may play a role in ischemia-induced neovascularization by recruiting macrophages that activate TNF-alpha and VEGF inductions.

PMID:
15358037
DOI:
10.1016/j.jacc.2004.04.046
[Indexed for MEDLINE]
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