IFN-gamma potentiates atherosclerosis in apoE knock-out mice
IFN-gamma potentiates atherosclerosis in apoE knock-out mice
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DOI：
10.1172/jci119465
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发表时间：
1997-06-01
影响因子：
15.9
通讯作者：
Schindler, C
中科院分区：
文献类型：
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作者：
Gupta, S;Pablo, AM;Schindler, C
T细胞和强效免疫刺激细胞因子IFN-γ对动脉粥样硬化病变的早期共定位表明免疫系统有助于动脉粥样硬化的发生。由于靶向破坏apoE基因的小鼠（apoE 0小鼠）会发生严重的动脉粥样硬化，因此我们检查了干扰素的作用-γ在这个过程中。首先，在apoE 0动脉粥样硬化中证实了分泌损伤性IFN-γ的CD 4（+）和CD 8（+）细胞的存在，然后，将apoE 0小鼠与IFN-γ受体与apoE 0小鼠相比，化合物敲除小鼠表现出动脉粥样硬化病变尺寸的显著减小，损伤脂质积聚减少60%，损伤细胞结构减少，但损伤胶原含量显著增加。血浆脂蛋白的评估显示，化合物敲除小鼠也具有潜在的动脉粥样硬化保护性磷脂/apoA-IV富集颗粒的显著增加。这与肝脏apoA-IV转录物的诱导相关。这些观察结果表明，IFN-γ通过动脉壁中的局部作用以及对血浆脂蛋白的全身作用促进和改变动脉粥样硬化。因此，IFN-γ信号传导的治疗性抑制可能导致形成更多的脂质贫乏和稳定的动脉粥样硬化。
The early colocalization of T cells and the potent immunostimulatory cytokine IFN-gamma to atherosclerotic lesions suggest that the immune system contributes to atherogenesis, Since mice with a targeted disruption of the apoE gene (apoE 0 mice) develop profound atherosclerosis, we examined the role of IFN-gamma in this process. First, the presence of CD4(+) and CD8(+) cells, which secrete lesional IFN-gamma, was documented in apoE 0 atheromata, Then, the apoE 0 mice were crossed with IFN-gamma receptor (IFN gamma R) 0 mice to generate apoE 0/IFN gamma R 0 mice, Compared to the apoE 0 mice, the compound knock-out mice exhibited a substantial reduction in atherosclerotic lesion size, a 60% reduction in lesion lipid accumulation, a decrease in lesion cellularity, but a marked increase in lesion collagen content. Evaluation of the plasma lipoproteins showed that the compound knockout mice had a marked increase in potentially atheroprotective phospholipid/apoA-IV rich particles as well. This correlated with an induction of hepatic apoA-IV transcripts, These observations suggest that IFN-gamma promotes and modifies atherosclerosis through both local effects in the arterial wall as well as a systemic effect on plasma lipoproteins. Therefore, therapeutic inhibition of IFN-gamma signaling may lead to the formation of more lipid-poor and stable atheromata.