Impact of modeled microgravity on microvascular endothelial cells
Impact of modeled microgravity on microvascular endothelial cells
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DOI：
10.1016/j.bbamcr.2005.10.002
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发表时间：
2005-12-15
影响因子：
5.1
通讯作者：
Maier, JAM
中科院分区：
文献类型：
--
作者：
Cotrupi, S;Ranzani, D;Maier, JAM
微血管内皮细胞是炎症和血管生成的主角。它们通过合成大量在内皮细胞、平滑肌细胞和循环白细胞上活跃的细胞因子、生长因子和介质来促进微血管系统的完整性。由于太空飞行 (i) 与血管损伤相关，并且 (ii) 调节细胞因子网络，因此我们评估了模拟微重力对微血管 1G11 细胞的影响。我们发现模拟微重力可逆地抑制内皮生长，这与细胞周期蛋白依赖性激酶抑制剂 p21 的上调相关。通过蛋白质阵列，我们发现微重力抑制白细胞介素 6 的合成，这一事件可能导致生长迟缓。我们还检测到一氧化氮含量增加，一氧化氮是炎症反应的介质、有效的血管扩张剂和血管生成的参与者。一氧化氮合成的增加至少部分归因于内皮一氧化氮合酶的上调。由于低水平的 IL-6 可能导致内皮生长迟缓以及一氧化氮合成的增强，因此我们假设 IL-6 在模拟微重力下调节微血管内皮细胞行为中发挥核心作用。 (c) 2005 Elsevier B.V. 保留所有权利。
Microvascular endothelial cells are protagonists in inflammation and angiogenesis. They contribute to the integrity of microvasculature by synthesizing a large array of cytokines, growth factors and mediators active on the endothelium, itself, on smooth muscle cells and circulating leukocytes. Because space flight (i) associates with vascular impairment and (ii) modulates the cytokine network, we evaluated the effect of modeled microgravity on microvascular 1G11 cells. We found that modeled microgravity reversibly inhibits endothelial growth and this correlates with an upregulation of p21, a cyclin-dependent kinases inhibitor. By protein array, we found that microgravity inhibits the synthesis of interleukin 6, an event that may contribute to growth retardation. We also detected increased amounts of nitric oxide, a mediator of inflammatory responses, a potent vasodilator and a player in angiogenesis. The increased synthesis of nitric oxide is due, at least in part, to an upregulation of endothelial nitric oxide synthase. Because low levels of IL-6 might contribute to endothelial growth retardation as well as to the enhancement of nitric oxide synthesis, we hypothesize a central role of IL-6 in modulating microvascular endothelial cell behaviour in modeled microgravity. (c) 2005 Elsevier B.V. All rights reserved.