Roles of endogenous monocyte chemoattractant protein-1 in ischemia-induced neovascularization
Roles of endogenous monocyte chemoattractant protein-1 in ischemia-induced neovascularization
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DOI：
10.1016/j.jacc.2004.04.046
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发表时间：
2004-08-04
影响因子：
24
通讯作者：
Imaizumi, T
中科院分区：
文献类型：
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作者：
Niiyama, H;Kai, H;Imaizumi, T
我们试图研究内源性单核细胞趋化蛋白（MCP）-1在缺血诱导的新生血管形成中的作用。背景包括巨噬细胞浸润在内的炎症变化在缺血性新生血管形成中的作用。对小鼠手术后立即将编码MCP-1显性失活突变体的质粒脱氧核糖核酸（7 ND）或空质粒（mock）注射到同侧大腿内收肌muscles.RESULTS在mock处理的小鼠中，MCP-1在缺血后肢短暂上调，在第3天达到峰值。连续激光多普勒血流（LDBF）分析显示，在模拟治疗小鼠的血流量突然减少，随后恢复到接近正常的水平; 7 ND治疗对LDBF的初始减少没有影响，但恶化了恢复。在第3天，巨噬细胞浸润和肿瘤坏死因子（TNF）-α和血管内皮生长因子（VEGF）的诱导在模拟治疗小鼠的缺血性闭肌中是突出的; 7 ND治疗显著减少巨噬细胞浸润和抑制TNF-α和VEGF诱导响应于缺血。在第21天，死后血管造影和抗CD 31 β染色显示发达的侧支血管和毛细血管形成，分别在模拟治疗小鼠的缺血肌肉; 7 ND过度表达显着抑制侧支血管形成和毛细血管形成。结论内源性MCP-1可能发挥作用，在缺血诱导的新生血管的招募激活TNF-α和VEGF诱导的巨噬细胞。(C)2004年，美国心脏病学会基金会。
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. (C) 2004 by the American College of Cardiology Foundation.