Cerebral angiogenic factors, angiogenesis, and physiological response to chronic hypoxia differ among four commonly used mouse strains
Cerebral angiogenic factors, angiogenesis, and physiological response to chronic hypoxia differ among four commonly used mouse strains
复制标题
DOI：
10.1152/japplphysiol.00909.2006
复制
发表时间：
2007-05-01
影响因子：
3.3
通讯作者：
LaManna, Joseph C.
中科院分区：
文献类型：
--
作者：
Ward, Nicole L.;Moore, Elizabeth;LaManna, Joseph C.
血管生成是适应低氧水平的关键因素，在大鼠长期暴露于轻度缺氧后发生。为了测试在小鼠中是否发生类似的反应，将CD1、129/Sv、C57B1/6和Balb/c小鼠暴露在10%的氧气中长达3wk。所有小鼠的红细胞压积百分比都显著增加，CD1和129/Sv小鼠的呼吸频率和每分钟容量增加，这是衡量低氧的常见生理指标。慢性缺氧3wk后，除Balb/c外，其余株系均可观察到明显的血管生成。CD1缺氧组增加最多(88%)，其次是C57B1/6(48%)、129/Sv(41%)和Balb/c(12%)，这表明一些小鼠在低氧条件下比其他小鼠经历了更多的重构。检测血管内皮生长因子(VEGF)、血管生成素(Ang)-1、Ang2和Tie2的蛋白表达，以确定不同的血管生成蛋白是否可以解释低氧诱导的血管生成的差异。CD1小鼠的血管内皮生长因子、血管紧张素转换酶2、血管紧张素转换酶1和Tie2的表达上调最强，而Balb/c小鼠的血管内皮生长因子只有轻微的增加，其他蛋白没有变化。C57B1/6小鼠表现出介于CD1和Balb/c小鼠之间的调节反应，与血管生成的中等增加一致。我们的结果表明，遗传异质性在血管生成和血管生成蛋白的调节中发挥作用，在设计和解释使用转基因小鼠的实验时，以及在研究血管生成的体内模型时，需要考虑到这一点。
Angiogenesis is a critical element for adaptation to low levels of oxygen and occurs following long-term exposure to mild hypoxia in rats. To test whether a similar response in mice occurs, CD1, 129/Sv, C57B1/6, and Balb/c mice were exposed to 10% oxygen for up to 3 wk. All mice showed significant increases in the percentage of packed red blood cells, and CD1 and 129/Sv mice showed increased respiration frequency and minute volume, common physiological measures of hypoxia. Significant angiogenesis was observed in all strains except Balb/c following 3-wk exposure to chronic hypoxia. CD1 hypoxic mice had the largest increase (88%), followed by C57B1/6 (48%), 129/Sv (41 %), and Balb/c (12%), suggesting that some mice undergo more remodeling than others in response to hypoxia. Protein expression analysis of vascular endothelial growth factor (VEGF), angiopoietin (Ang)-1 and Ang2, and Tie2 were examined to determine whether regulation of different angiogenic proteins could account for the differences observed in hypoxia-induced angiogenesis. CD1 mice showed the strongest upregulation of VEGF, Ang2, Ang1, and Tie2, whereas Balb/c had only subtle increases in VEGF and no change in the other proteins. C57B1/6 mice showed a regulatory response that fell between the CD1 and Balb/c mice, consistent with the intermediate increase in angiogenesis. Our results suggest that genetic heterogeneity plays a role in angiogenesis and regulation of angiogenic proteins and needs to be accounted for when designing and interpreting experiments using transgenic mice and when studying in vivo models of angiogenesis.