Ultrasound Biomicroscopic Imaging for Interleukin-1 Receptor Antagonist-Inhibiting Atherosclerosis and Markers of Inflammation in Atherosclerotic Development in Apolipoprotein-E Knockout Mice
Ultrasound Biomicroscopic Imaging for Interleukin-1 Receptor Antagonist-Inhibiting Atherosclerosis and Markers of Inflammation in Atherosclerotic Development in Apolipoprotein-E Knockout Mice
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DOI：
10.14503/thij-14-4318
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发表时间：
2015-08-01
影响因子：
0.9
通讯作者：
Su, Rui-Juan
中科院分区：
文献类型：
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作者：
Li, Rong-Juan;Sun, Yan;Su, Rui-Juan
为了验证白介素1受体拮抗剂(IL-1ra)可以抑制小鼠动脉粥样硬化发展的假说，通过高分辨率超声生物显微镜非侵入性观察，我们研究了IL-1和C反应蛋白(CRP)等炎症标记物在这些动脉粥样硬化模型中的变化。我们将IL-1ra(+/-)/apoE(-/-)和IL-1ra(+/+)/apoE(-/-)小鼠分为两个年龄组，作为动脉粥样硬化模型。对照组为年龄匹配的IL-1ra(+/+)/apoE(+/+)小鼠。超声和组织学方法测量升主动脉短轴图像斑块厚度。16周时，超声和组织学显示IL-1ra(+/-)/apoE(-/-)组小鼠升主动脉斑块厚度明显大于IL-1ra(+/+)/apoE(-/-)组(P<；0.01)。相反，在32周时，这两种基因型之间的差异没有统计学意义。16周和32周时，IL-1ra(+/-)/apoE(-/-)组小鼠血清IL-1水平低于IL-1ra(+/+)/apoE(-/-)组(P<；0.05)。在16周时，IL-1Ra(+/-)/apoE(-/-)小鼠的血清CRP水平高于IL-1ra(+/+)/apoE(-/-)小鼠(P<；0.01)。我们的结果表明，超声生物显微镜能够在体内、无创和实时地评估apoE(-/-)小鼠的动脉粥样硬化病变。部分IL-1ra缺乏可能促进16周龄apoE(-/-)小鼠早期斑块的形成。IL-1和IL-1ra的平衡可能影响动脉粥样硬化的发展。最后，CRP可能影响动脉粥样硬化的启动，而不是其进展。
We sought to validate the hypothesis that the development of atherosclerosis can be suppressed by the interleukin-1 receptor antagonist (IL-1Ra) in murine models of atherosclerosis in vivo, noninvasively seen by means of high-resolution ultrasound biomicroscopy, and we studied changes in inflammatory markers such as IL-1 and C-reactive protein (CRP) plasma levels in these models of atherosclerosis.We divided IL-1Ra(+/-)/apolipoprotein-E (apoE)(-/-) and IL-1Ra(+/+)/apoE(-/-) mice into 2 age groups, used as atherosclerotic models. The control groups were age-matched IL-1Ra(+/+)/apoE(+/+) mice. Plaque thickness was measured in the ascending aorta in short-axis images by means of ultrasound and histology. Plasma levels of IL-1 and CRP were quantified in the 3 murine groups.At 16 weeks, plaque thickness in the ascending aortas of the IL-1Ra(+/-)/apoE(-/-) mice was significantly greater than that in the IL-1Ra(+/+)/apoE(-/-) mice, on ultrasound and histology (P < 0.01). In contrast, at 32 weeks, the differences between these 2 genotypes were not statistically significant. Serum IL-1 levels were lower in the IL-1Ra(+/-)/apoE(-/-) mice than in the IL-1Ra(+/+)/apoE(-/-) mice at 16 and 32 weeks (P < 0.05). At 16 weeks, serum CRP levels in the IL-1Ra(+/-)/apoE(-/-) mice were higher than in the IL-1Ra(+/+)/apoE(-/-) mice (P < 0.01).Our results suggest that ultrasound biomicroscopy enables evaluation of atherosclerotic lesions in vivo, noninvasively and in real-time, in apoE(-/-) mice. Partial IL-1Ra deficiencies might promote early plaque development in 16-week-old apoE(-/-) mice. The balance of IL-1 and IL-1Ra might influence atherosclerotic development. Finally, CRP might affect the initiation of atherosclerosis, rather than its progression.