Shoji Makoto, Furuyama Fumiaki, Yokota Yuya, Omori Yasutoshi, Sato Takatoshi, Tsunoda Fumiyoshi, Iso Yoshitaka, Koba Shinji, Geshi Eiichi, Katagiri Takashi, Suzuki Hiroshi, Kobayashi Youichi
Department of Medicine, Division of Cardiology, Showa University School of Medicine.
J Atheroscler Thromb. 2014;21(4):304-12. doi: 10.5551/jat.19414. Epub 2013 Dec 20.
Among the many factors related to bone marrow cell mobilization, local inflammation induced by cytokines may drive bone marrow cells to the vascular wall, resulting in a thickened neointima. However, the relationship between inflammatory reactions and bone marrow cell invasion has not yet been fully clarified.
We inserted a large wire into the femoral artery in male balb/c(WT), interleukin (IL)-6-knockout (KO) and bone marrow-transplanted (BMT) mice that had received bone marrow cells from KO mice. Immunohistochemistry was performed to evaluate the degree of intimal hyperplasia and inflammation following vascular injury.
Three days after the vascular injury, the number of CD34/Sca-1-positive cells in the blood was higher in the KO mice. The numbers of apoptotic cells in the neointima was lower in the KO and BMT mice at two hours after injury. The morphometric analysis performed at one and four weeks after injury showed that the intima/media ratio was significantly lower in the KO and BMT mice, while CD34-positive cells were much more frequent in the WT mice. Furthermore, re-endothelialization appeared earlier in the KO and BMT mice than in the WT mice. No differences in the levels of vascular endothelial growth factor or hepatocyte growth factor were observed in the mice sera between the WT, KO and BMT mice after injury. The in vitro culture of bone marrow cells showed more differentiated smooth muscle-like cells in the WT mice than in the KO mice.
IL-6 is involved in neointimal formation following vascular injury, possibly acting through inflammatory effects inducing the production of bone marrow cells.
在与骨髓细胞动员相关的众多因素中，细胞因子诱导的局部炎症可能会促使骨髓细胞迁移至血管壁，导致新生内膜增厚。然而，炎症反应与骨髓细胞浸润之间的关系尚未完全阐明。
我们将一根粗线插入雄性balb/c（野生型）、白细胞介素（IL）-6基因敲除（KO）以及接受了来自KO小鼠骨髓细胞的骨髓移植（BMT）小鼠的股动脉。采用免疫组织化学方法评估血管损伤后内膜增生和炎症程度。
血管损伤后3天，KO小鼠血液中CD34/Sca-1阳性细胞数量更高。损伤后2小时，KO小鼠和BMT小鼠新生内膜中的凋亡细胞数量较少。损伤后1周和4周进行的形态计量分析显示，KO小鼠和BMT小鼠的内膜/中膜比值显著更低，而野生型小鼠中CD34阳性细胞更为常见。此外，KO小鼠和BMT小鼠的再内皮化比野生型小鼠出现得更早。损伤后，野生型、KO和BMT小鼠的血清中血管内皮生长因子或肝细胞生长因子水平未观察到差异。骨髓细胞的体外培养显示，野生型小鼠中分化为平滑肌样细胞的数量比KO小鼠更多。
IL-6参与血管损伤后的新生内膜形成，可能通过诱导骨髓细胞产生的炎症效应发挥作用。
