Bone Marrow-Derived Cells Contribute to Vascular Inflammation but Do Not Differentiate Into Smooth Muscle Cell Lineages
Bone Marrow-Derived Cells Contribute to Vascular Inflammation but Do Not Differentiate Into Smooth Muscle Cell Lineages
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DOI：
10.1161/circulationaha.110.965202
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发表时间：
2010-11-16
期刊：
影响因子：
37.8
通讯作者：
Nagai, Ryozo
中科院分区：
文献类型：
--
作者：
Iwata, Hiroshi;Manabe, Ichiro;Nagai, Ryozo
背景——有人提出，骨髓来源的细胞浸润新内膜，并在那里分化成平滑肌（SM）细胞；然而，技术限制阻碍了对骨髓来源的“SM细胞样”细胞谱系的明确鉴定。 方法和结果-使用针对明确的SM细胞谱系标记物SM肌球蛋白重链（SM-MHC）的特异性抗体和报告基因由SM-MHC或SM α-肌动蛋白的调节程序驱动的小鼠品系，我们证明，尽管一些骨髓来源的细胞表达SM α-肌动蛋白在线损伤诱导的新内膜中，这些细胞即使在损伤后 30 周也不表达 SM-MHC。同样，在载脂蛋白E-/-小鼠的血管病变或心脏移植血管病变模型中也没有发现SM-MHC+骨髓来源的细胞。相反，大多数骨髓来源的 SM α-肌动蛋白 (+) 细胞也是 CD115(+)CD11b(+)F4/80(+)Ly-6C(+)，这是炎症单核细胞的表面表型。此外，过继转移的CD11b(+)Ly-6C(+)骨髓细胞在受伤动脉中表达SM α-肌动蛋白。富含骨髓源性 SM α-actin(+) 细胞的新生内膜亚区域炎症相关基因的表达显着高于其他区域。 结论：骨髓源性 SM α-actin(+) 细胞属于单核/巨噬细胞谱系，参与血管重塑。这些细胞不太可能获得最终的 SM 细胞谱系。 （流通。2010 年；122：2048-2057。）
Background-It has been proposed that bone marrow-derived cells infiltrate the neointima, where they differentiate into smooth muscle (SM) cells; however, technical limitations have hindered clear identification of the lineages of bone marrow-derived "SM cell-like" cells.Methods and Results-Using a specific antibody against the definitive SM cell lineage marker SM myosin heavy chain (SM-MHC) and mouse lines in which reporter genes were driven by regulatory programs for either SM-MHC or SM alpha-actin, we demonstrated that although some bone marrow-derived cells express SM alpha-actin in the wire injury-induced neointima, those cells did not express SM-MHC, even 30 weeks after injury. Likewise, no SM-MHC+ bone marrow-derived cells were found in vascular lesions in apolipoprotein E-/- mice or in a heart transplantation vasculopathy model. Instead, the majority of bone marrow-derived SM alpha-actin(+) cells were also CD115(+)CD11b(+)F4/80(+)Ly-6C(+), which is the surface phenotype of inflammatory monocytes. Moreover, adoptively transferred CD11b(+)Ly-6C(+) bone marrow cells expressed SM alpha-actin in the injured artery. Expression of inflammation-related genes was significantly higher in neointimal subregions rich in bone marrow-derived SM alpha-actin(+) cells than in other regions.Conclusions-It appears that bone marrow-derived SM alpha-actin(+) cells are of monocyte/macrophage lineage and are involved in vascular remodeling. It is very unlikely that these cells acquire the definitive SM cell lineage. (Circulation. 2010; 122: 2048-2057.)