Study on the mechanism of atherosclerotic lesion formation using cytokine-knockout mouse
Study on the mechanism of atherosclerotic lesion formation using cytokine-knockout mouse
批准号:
13470517
负责人:
SEISHIMA Mitsuru
金额:
$8.7万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B)
财政年份:
2001
资助国家:
日本
项目状态:
已结题
起止时间:
2001 至 2003
中文摘要
1.在肿瘤坏死因子-α;-/->;-/->;双KO小鼠与apoE^<;-/->;KO小鼠的比较研究中,双KO小鼠动脉粥样硬化病变面积明显缩小。此外,ICAM-1和VCAM-1等黏附分子在双KO小鼠体内的表达也受到明显抑制。这些结果提示,黏附分子的表达增强至少部分参与了肿瘤坏死因子-α的动脉粥样硬化作用。2.与载脂蛋白E^<;-/->;-/->;双重γ小鼠相比,双重ko小鼠的动脉粥样硬化病变明显减轻,细胞间黏附分子-1和血管细胞间黏附分子-1的表达水平显著降低。提示IL-1β可将包括单核细胞在内的单个核细胞聚集到动脉壁上,导致动脉粥样硬化病变的形成。3.在主动脉窦、主动脉弓和腹主动脉,干扰素-γ;-/->;BMT小鼠的动脉粥样硬化病变比干扰素-γ^-+>;这些结果表明,骨髓源性细胞产生的干扰素-γ在不影响血脂的情况下延缓了动脉粥样硬化的进展,这种抑制可能是由于减少了细胞外基质的沉积。在本研究中,我们阐明了肿瘤坏死因子-α和IL-1β通过促进体内黏附分子的表达来加速动脉粥样硬化。然而,骨髓来源的干扰素-γ至少在早期阶段对动脉粥样硬化有一定的抑制作用。
英文摘要
1.In the study on the comparison of TNF-α^<-/-> apoE^<-/-> double KO mouse with apoE^<-/-> KO mice, the area of atherosclerotic lesion was significantly reduced in double KO mice. In addition, the expression of adhesion molecules such as ICAM-1and VCAM-1was also significantly suppressed in double KO mouse. These fidings suggest that augumented expression of adhesion molecules is, at least in part, involved in the atherosclerotic action of TNF-α.2.The atherosclerotic lesion was significantly reduced in IFN-γ^<-/-> apoE^<-/-> double KO mice compared with apoE^<-/-> KO mice and mRNA levels of ICAM-1 and VCAM-1 were significantly decreased in double KO mice. It is suggested that mononuclear cells including monocytes are recruited to arterial wall by IL-1β, resulting in the formation of atherosclerotic lesion.3.The atherosclerotic lesions of IFN-γ^<-/->BMT mice were larger than those of IFN-γ^<+/+>BMT mice at the aortic sinus, aortic arch and abdominal aorta. These findings show that IFN-γ produced by bone marrow-derived cells delays the progression of atherosclerosis without any effects on plasma lipids, and this suppression may be due to decreased extracellular matrix deposition.In this study, we clarified that TNF-α and IL-1β accelerate atherosclerosis via the augumented expression of adhesion molecules in vivo study. However, IFN-y derived from bone marrow rather suppressed atherosclerosis at least in the initial stage.
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清島 満 他: "臨床検査項辞典"医歯薬出版株式会社. 219-225 (2003)
Mitsuru Kiyoshima等:《临床试验词典》石药出版有限公司219-225(2003)
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通讯作者:
Fujigaki S, et al.: "L-tryptophan-L-Kynurenine pathway metabolism accelerated by Toxoplasma gondii infection is abolished in gamma interferon-gene-deficient mice : cross-regulation between Inducible nitric oxide Synthase and indoleamine-2,3-dioxygenas"Inf
Fujigaki S 等人:“弓形虫感染加速的 L-色氨酸-L-犬尿氨酸途径代谢在γ干扰素基因缺陷小鼠中被消除:诱导型一氧化氮合酶和吲哚胺-2,3-双加氧酶之间的交叉调节”
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Niwa T, et al.: "Interferon-γ produced by bone marrow-derived cells attenuates atherosclerotic lesion formation in LDLR-deficient mice"J Atheroscler Thromb. 11. 80-89 (2004)
Niwa T 等人:“骨髓来源细胞产生的干扰素-γ 可减弱 LDLR 缺陷小鼠的动脉粥样硬化病变形成”J Atheroscler Thromb. 11. 80-89 (2004)
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Iwasaki M, et al.: "Tumor necrosis factor-alpha from bone marrow-derived cells is not essential for the expression of adhesion molecules in lipopolysaccharide-induced nasal inflammation."Cytokine. 21(3). 129-136 (2003)
Iwasaki M 等人:“来自骨髓来源细胞的肿瘤坏死因子-α 对于脂多糖诱导的鼻部炎症中粘附分子的表达并不是必需的。”细胞因子。
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Maekawa N., et al.: "Improved myocardial ischemia/reperfusion injury in mice lacking tumor necrosis factor-α"J. Am. Coll. Cardiol.. 39. 1229-1235 (2002)
Maekawa N. 等人:“改善缺乏肿瘤坏死因子-α 的小鼠的心肌缺血/再灌注损伤”J. Am. Cardiol.. 39. 1229-1235 (2002)
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海外基金