Regulation of the migration and survival of monocyte subsets by chemokine receptors and its relevance to atherosclerosis.
Regulation of the migration and survival of monocyte subsets by chemokine receptors and its relevance to atherosclerosis.
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DOI：
10.1161/atvbaha.108.180505
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发表时间：
2009-10
期刊：
影响因子：
--
通讯作者：
Randolph GJ
中科院分区：
文献类型：
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作者：
Gautier EL;Jakubzick C;Randolph GJ
单核细胞是动脉粥样硬化斑块进展的中心介质，使其成为减少疾病负担的天然治疗靶点。在这里，我们强调了我们目前对单核细胞异质性及其与动脉粥样硬化斑块内单核细胞聚集和功能调节相关性的理解的最新进展。区分单核细胞亚群的差异包括趋化因子受体的差异表达，特别是CCR 2和CX 3CR 1。在小鼠中，这两种受体（或其配体）的表达的消融对单核细胞向动脉粥样硬化斑块的募集具有叠加抑制作用。此外，同时干扰三个关键途径-CCR 2，CX 3CR 1和CCR 5-基本上消除了小鼠的动脉粥样硬化。在这里，我们讨论了这些趋化因子受体如何在多个点作用于至少一个单核细胞亚群，调节它们从骨髓中的动员，存活和/或斑块的招募。最后，我们讨论了这些知识如何在临床上有用，强调CX 3CR 1可能特别是一个可行的目标，在心血管疾病的单核细胞衍生的细胞命运的治疗操作。
Monocytes are central mediators in the advance of atherosclerotic plaque, making them a natural therapeutic target for reducing disease burden. Here, we highlight recent advances in our current understanding of monocyte heterogeneity and its relevance to regulation of monocyte accumulation and function within atherosclerotic plaques. Differences that distinguish monocyte subsets include differential expression of chemokine receptors, especially CCR2 and CX3CR1. Ablation of expression of these two receptors (or their ligands) in mice has an additive inhibition on monocyte recruitment to atherosclerotic plaques. Moreover, simultaneously interfering with three key pathways—CCR2, CX3CR1, and CCR5--essentially abolishes atherosclerosis in mice. Here, we discuss how these chemokine receptors act at multiple points on at least one monocyte subset, regulating their mobilization from bone marrow, survival, and/or recruitment to plaques. Finally, we discuss how this knowledge may be useful clinically, emphasizing that CX3CR1 may in particular be a viable target for therapeutic manipulation of monocyte-derived cell fate in cardiovascular disease.