Vascular inflammation in absence of blood pressure elevation in transgenic murine model overexpressing endothelin-1 in endothelial cells
Vascular inflammation in absence of blood pressure elevation in transgenic murine model overexpressing endothelin-1 in endothelial cells
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DOI：
10.1097/hjh.0b013e3282fc2184
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发表时间：
2008-06-01
影响因子：
4.9
通讯作者：
Schiffrin, Ernesto L.
中科院分区：
文献类型：
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作者：
Amiri, Farhad;Paradis, Pierre;Schiffrin, Ernesto L.
目的我们先前的研究表明，在内皮靶向过表达人前内皮素-1的转基因小鼠中，肠系膜阻力动脉在生命早期表现出血管重构、内皮功能障碍和氧化应激增加，而血压没有明显升高。方法和结果采用Luminex酶联免疫吸附分析技术、共聚焦显微镜、凝胶迁移率改变分析和免疫印迹等方法检测了10周龄转基因和野生型雄性小鼠肠系膜动脉局部和全身炎症标志物的表达。尽管在全身炎症标志物方面没有发现差异，但单核细胞趋化蛋白-1的血管染色和巨噬细胞的浸润在转基因小鼠与野生型小鼠相比显著增加(P<；0.05)。与野生型小鼠相比，转基因小鼠在转录因子激活蛋白-1和核因子kappa B的激活方面表现出显著的提高(P<；0.01)。Western blotting分析显示转基因小鼠血管壁血管细胞黏附分子-1的表达显著增加(P<；0.05)。结论在这种内皮细胞限制性的前内皮素-1过表达的小鼠模型中，内皮素-1在没有血压升高或全身炎症的情况下，通过多条途径诱导幼年动物的血管炎症。
Objective We previously showed that in transgenic mice with endothelium-targeted overexpression of human preproendothelin-1, mesenteric resistance arteries exhibited vascular remodeling, endothelial dysfunction and increased oxidative stress early in life in the absence of significant elevation of blood pressure. To further characterize this model, the role of vascular inflammation was investigated in young male transgenic and wild-type littermate mice.Methods and results Systemic and local inflammatory markers in mesenteric arteries were assessed by Luminex-based enzyme-linked immunosorbent assay technique, confocal microscopy, electrophoretic mobility shift assay and western blotting in 10-week old male transgenic and wild-type mice. Although no differences were found for systemic inflammatory markers, vascular staining for monocyte chemoattractant protein-1 and macrophage infiltration were significantly increased (P < 0.05) in transgenic mice compared with wild-type littermates. Transgenic mice exhibited significant increase (P < 0.01) in the activation of transcription factors activator protein-1 and nuclear factor kappa B compared with wild-type littermates. Western blotting analysis showed significantly increased (P < 0.05) blood vessel wall expression of vascular cell adhesion molecule-1 in transgenic mice.Conclusion These findings suggest that in this murine model of endothelial cell-restricted preproendothelin-1 overexpression, endothelin-1 induces vascular inflammation by multiple pathways in young animals in the absence of blood pressure elevation or systemic inflammation.