Yuan Falei, Wang Dong, Xu Kang, Wang Jixian, Zhang Zhijun, Yang Li, Yang Guo-Yuan, Li Song
Department of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
PLoS One. 2017 Jan 6;12(1):e0168914. doi: 10.1371/journal.pone.0168914. eCollection 2017.
The de-differentiation and proliferation of smooth muscle cells (SMCs) are widely accepted as the major contributor to vascular remodeling. However, recent studies indicate that vascular stem cells (VSCs) also play an important role, but their relative contribution remains to be elucidated. In this study, we used genetic lineage tracing approach to further investigate the contribution of SMCs and VSCs to neointimal thickening in response to endothelium denudation injury or artery ligation. In vitro and in vivo analysis of MYH11-cre/Rosa-loxP-RFP mouse artery showed that SMCs proliferated at a much slower rate than non-SMCs. Upon denudation or ligation injury, two distinct types of neointima were identified: Type-I neointimal cells mainly involved SMCs, while Type II mainly involved non-SMCs. Using Sox10-cre/Rosa-loxP-LacZ mice, we found that Sox10+ cells were one of the cell sources in neointima. In addition, lineage tracing using Tie2-cre/Rosa-LoxP-RFP showed that endothelial cells also contributed to the neointimal formation, but rarely transdifferentiated into mesenchymal lineages. These results provide a novel insight into the contribution of vascular cells to neointima formation, and have significant impact on the development of more effective therapies that target specific vascular cell types.
平滑肌细胞（SMC）的去分化和增殖被广泛认为是血管重塑的主要促成因素。然而，最近的研究表明血管干细胞（VSC）也发挥着重要作用，但其相对贡献仍有待阐明。在本研究中，我们使用遗传谱系追踪方法进一步研究SMC和VSC对内皮剥脱损伤或动脉结扎后新生内膜增厚的贡献。对MYH11-cre/Rosa-loxP-RFP小鼠动脉进行体外和体内分析表明，SMC的增殖速度比非SMC慢得多。在剥脱或结扎损伤后，鉴定出两种不同类型的新生内膜：I型新生内膜细胞主要涉及SMC，而II型主要涉及非SMC。使用Sox10-cre/Rosa-loxP-LacZ小鼠，我们发现Sox10+细胞是新生内膜中的细胞来源之一。此外，使用Tie2-cre/Rosa-LoxP-RFP进行谱系追踪表明，内皮细胞也参与了新生内膜的形成，但很少转分化为间充质谱系。这些结果为血管细胞对新生内膜形成的贡献提供了新的见解，并对开发针对特定血管细胞类型的更有效疗法具有重大影响。
