Interleukin-18/interleukin-18 binding protein signaling modulates atherosclerotic lesion development and stability
Interleukin-18/interleukin-18 binding protein signaling modulates atherosclerotic lesion development and stability
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DOI：
10.1161/hh1901.098735
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发表时间：
2001-09-28
影响因子：
20.1
通讯作者：
Tedgui, A
中科院分区：
文献类型：
--
作者：
Mallat, Z;Corbaz, A;Tedgui, A
白介素 (IL)-18 是干扰素-γ 诱导因子，并具有其他促炎特性。 IL-18 在免疫炎症疾病中的确切作用仍知之甚少。在这项研究中，我们发现编码鼠IL-18结合蛋白（BP）（IL-18的内源性抑制剂）的表达质粒DNA的体内电转移可以防止apoE基因敲除小鼠胸主动脉中脂肪条纹的形成，并减缓主动脉窦中晚期动脉粥样硬化斑块的进展。更重要的是，用IL-18BP质粒转染可引起斑块组成的深刻变化（巨噬细胞、T细胞、细胞死亡和脂质含量减少，平滑肌细胞和胶原含量增加），从而形成稳定的斑块表型。这些结果首次确定了 IL-18/IL-18BP 调节在动脉粥样硬化中的关键作用，并表明 IL-18 抑制剂在减少斑块发展/进展和促进斑块稳定性方面具有潜在作用。本文全文可在 http://www.circresaha.org 上获取。
Interleukin (IL)-18 is the interferon-γ–inducing factor and has other proinflammatory properties. The precise role of IL-18 in immunoinflammatory diseases remains poorly understood. In this study, we show that in vivo electrotransfer of an expression-plasmid DNA encoding for murine IL-18 binding protein (BP) (the endogenous inhibitor of IL-18) prevents fatty streak development in the thoracic aorta of apoE knockout mice and slows progression of advanced atherosclerotic plaques in the aortic sinus. More importantly, transfection with the IL-18BP plasmid induces profound changes in plaque composition (decrease in macrophage, T cell, cell death, and lipid content and increase in smooth muscle cell and collagen content) leading to a stable plaque phenotype. These results identify for the first time a critical role for IL-18/IL-18BP regulation in atherosclerosis and suggest a potential role for IL-18 inhibitors in reduction of plaque development/progression and promotion of plaque stability. The full text of this article is available at http://www.circresaha.org.