VEGFR-1-selective VEGF homologue PlGF is arteriogenic -: Evidence for a monocyte-mediated mechanism
VEGFR-1-selective VEGF homologue PlGF is arteriogenic -: Evidence for a monocyte-mediated mechanism
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DOI：
10.1161/01.res.0000057997.77714.72
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发表时间：
2003-03-07
影响因子：
20.1
通讯作者：
Clauss, M
中科院分区：
文献类型：
--
作者：
Pipp, F;Heil, M;Clauss, M
已知血管系统中血管内皮生长因子（VEGF）的两种信号传导受体在侧支血管生长（动脉生成）中的作用尚不清楚。在这项研究中，我们研究了两种VEGF受体参与动脉形成。因此，我们使用了VEGF同源物胎盘生长因子（PlGF），其仅结合VEGFR-1和VEGF-E，其仅识别VEGFR-2。这些肽在兔股动脉结扎后7天内局部输注。通过确定侧支传导和血管造影评分评估侧支生长表明，VEGFR-1特异性PlGF比VEGFR-2特异性VEGF-E对动脉生成的贡献显著更多。VEGF-E和PlGF的组合没有超过单独的PlGF的作用，表明两种VEGF受体在内皮细胞信号传导中的合作对于动脉生成是不需要的。在血管生成的体外模型中，VEGF和VEGF-E具有抑制活性，而PlGF单独给药时没有显示活性，并且没有进一步增加VEGF或VEGF-E的作用。然而，当通过监测整合素表面表达评估单核细胞活化时，PlGF与VEGF一样有效。此外，观察到活化的单核细胞/巨噬细胞在PlGF处理的动物中的侧支血管的外周中的积累。此外，在单核细胞耗尽的动物中，PlGF增强兔模型中侧支生长和拯救PlGF基因缺陷小鼠中受损的动脉生成的能力被消除。总之，这些数据表明，用VEGFR-1特异性PlGF观察到的动脉生成活性是由其单核细胞活化特性引起的。
Two signaling receptors for vascular endothelial growth factor (VEGF) in the vasculature are known with not yet well-understood roles in collateral vessel growth (arteriogenesis). In this study, we examined the involvement of the two VEGF receptors in arteriogenesis. Therefore, we used the VEGF homologue placenta growth factor (PlGF), which only binds to VEGFR-1 and VEGF-E, which only recognizes VEGFR-2. These peptides were locally infused over 7 days after ligation of the femoral artery in the rabbit. Evaluation of collateral growth by determining collateral conductance and angiographic scores demonstrated that the VEGFR-1-specific PlGF contributed significantly more to arteriogenesis than the VEGFR-2 specific VEGF-E. The combination of VEGF-E and PlGF did not exceed the effect of PlGF alone, indicating that cooperation of the two VEGF receptors in endothelial cell signaling is not required for arteriogenesis. In an in vitro model of angiogenesis, VEGF and VEGF-E were comparably active, whereas PlGF displayed no activity when given alone and did not further increase the effects of VEGF or VEGF-E. However, PlGF was as potent as VEGF when monocyte activation was assessed by monitoring integrin surface expression. In addition, accumulation of activated monocytes/macrophages in the periphery of collateral vessels in PlGF-treated animals was observed. Furthermore, in monocyte-depleted animals, the ability of PlGF to enhance collateral growth in the rabbit model and to rescue impaired arteriogenesis in PlGF gene-deficient mice was abrogated. Together, these data indicate that the arteriogenic activity observed with the VEGFR-1-specific PlGF is caused by its monocyte-activating properties.