Cardiovascular Division, King's College London BHF Centre, 125 Coldharbour Lane, London SE5 9NU, UK.
John Moorhead Research Laboratory, Centre for Nephrology, University College London, Rowland Hill Street, London NW3 2PF, UK.
Stem Cell Reports. 2017 Aug 8;9(2):681-696. doi: 10.1016/j.stemcr.2017.06.011. Epub 2017 Jul 27.
Adventitial progenitor cells, including SCA-1 and mesenchymal stem cells, are believed to be important in vascular remodeling. It has been shown that SCA-1 progenitor cells are involved in neointimal hyperplasia of vein grafts, but little is known concerning their involvement in hyperlipidemia-induced atherosclerosis. We employed single-cell sequencing technology on primary adventitial mouse SCA-1 cells from wild-type and atherosclerotic-prone (ApoE-deficient) mice and found that a group of genes controlling cell migration and matrix protein degradation was highly altered. Adventitial progenitors from ApoE-deficient mice displayed an augmented migratory potential both in vitro and in vivo. This increased migratory ability was mimicked by lipid loading to SCA-1 cells. Furthermore, we show that lipid loading increased miRNA-29b expression and induced sirtuin-1 and matrix metalloproteinase-9 levels to promote cell migration. These results provide direct evidence that blood cholesterol levels influence vascular progenitor cell function, which could be a potential target cell for treatment of vascular disease.
血管外膜祖细胞，包括 SCA-1 和间充质干细胞，被认为在血管重塑中起重要作用。已经表明 SCA-1 祖细胞参与静脉移植物的新生内膜增生，但对于它们在高脂血症诱导的动脉粥样硬化中的作用知之甚少。我们使用单细胞测序技术对来自野生型和易患动脉粥样硬化的（载脂蛋白 E 缺陷）小鼠的原代血管外膜 SCA-1 细胞进行了研究，发现一组控制细胞迁移和基质蛋白降解的基因发生了高度改变。载脂蛋白 E 缺陷小鼠的血管外膜祖细胞在体外和体内都表现出增强的迁移潜力。脂质负荷可模拟 SCA-1 细胞的这种迁移能力增强。此外，我们表明，脂质负荷增加了 miRNA-29b 的表达，并诱导了沉默调节蛋白 1 和基质金属蛋白酶-9 的水平，从而促进细胞迁移。这些结果提供了直接证据，表明血液胆固醇水平影响血管祖细胞功能，这可能是治疗血管疾病的潜在靶细胞。
