Inhibition of Atherosclerosis by a Cytokine Signal Suppressor Molecule JAB/SOCS-1/SSI-I

细胞因子信号抑制分子 JAB/SOCS-1/SSI-I 抑制动脉粥样硬化

• 批准号: 15590739
• 负责人: FURUKAWA Yutaka
• 金额: $ 2.24万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590739/
• 关键词: Cytokine; Suppressor of Signaling; Atherosclerosis

To investigate whether enhanced expression of JAK-binding protein/suppressor of cytokine signaling 1/STAT induced STAT-inhibitor 1(JAB/SOCS-1/SSI-1) in macrophages could prevent the development of atherosclerotic lesions, JAB over-expressing apolipoprotein E-deficient mice (JAB Tg/apoE^<-/->) were generated by crossing CD11b promoter driven JAB transgenic mice (JAB Tg) and apoE^<-/-> mice.Four JAB Tg/apoE^<-/-> and 8 JAB WT/apoE^<-/-> mice were sacrificed at 30 weeks of age and en face quantification of atherosclerotic lesions in the aorta was performed by measuring percentage of oil red-O positive area to whole aortic luminal surface area for each mouse. The percent oil red-O positive area tended to be reduced in JAB Tg/apoE^<-/-> mice (16.9±2.7^<-/-> ; mean±SD) relative to JAB WT/apoE^<-/-> mice (p=0.07).Total serum cholesterol (T-CHO) and triglyceride levels (TG) were both comparable between the two groups : T-CHO of JAB WT/apoE^<-/-> vs. JAB Tg/apoE^<-/-> mice=530±102 mg/dL vs. 434±28 mg/dL, TG of JAB WT/apoE^<-/-> vs. JAB Tg/apoE^<-/-> mice=110±51 mg/dL vs. 95±32 mg/dL.Thus, enhanced expression of JAB in macrophages might have beneficial effects in the inhibition of atherosclerosis. The effects appeared to be independent of lipid profile modification.

研究JAK结合蛋白/细胞因子信号传导抑制因子1/STAT的表达增强是否诱导STAT抑制因子1（JAB/SOCS-1/SSI-1）可以阻止动脉粥样硬化病变的发展，JAB过表达载脂蛋白E缺陷小鼠通过将CD 11b启动子驱动的JAB转基因小鼠（JAB Tg）和apoE^<-/->小鼠杂交来产生JAB Tg/apoE ^<-/->小鼠。在30周龄时处死-/->小鼠，并通过测量每只小鼠的油红-O阳性面积与整个主动脉腔表面积的百分比来进行主动脉中动脉粥样硬化病变的正面定量。油红-O阳性面积百分比在JAB Tg/apoE^<-/->小鼠中倾向于减少（16.9±2.7^<-/-> ;平均值±SD），相对于JAB WT/apoE^<-/->小鼠（p=0.07）。两组之间的总血清胆固醇（T-CHO）和甘油三酯水平（TG）均相当：JAB WT/apoE^<-/->与JAB Tg/apoE^<-/->小鼠的T-CHO =530±102 mg/dL与434±28 mg/dL，JAB WT/apoE^<-/->与JAB Tg/apoE^<-/->小鼠的TG =110±51 mg/dL与95±32 mg/dL。巨噬细胞中JAB表达增强可能具有抑制动脉粥样硬化的有益作用。这些作用似乎与血脂改变无关。