Overexpression of TGF-ß1 in Macrophages Reduces and Stabilizes Atherosclerotic Plaques in ApoE-Deficient Mice
Overexpression of TGF-ß1 in Macrophages Reduces and Stabilizes Atherosclerotic Plaques in ApoE-Deficient Mice
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巨噬细胞中 TGF-β1 的过度表达可减少和稳定 ApoE 缺陷小鼠的动脉粥样硬化斑块
作者：
K. Reifenberg;F. Cheng;C. Orning;Jeanine Crain;Ines Küpper;Elena Wiese;M. Protschka;M. Blessing;K. Lackner;M. Torzewski
尽管巨噬细胞是人和小鼠动脉粥样硬化病变的标志，并且已被证明表达TGF-ß1（转化生长因子β1）及其受体，但迄今尚未通过实验解决多效细胞因子TGF-ß1是否通过巨噬细胞特异性机制影响动脉粥样硬化的发生。我们培育巨噬细胞特异性TGF-ß1过表达的转基因小鼠，将转基因与动脉粥样硬化ApoE（载脂蛋白E）敲除菌株杂交，并定量分析动脉粥样硬化病变的发展和由此产生的双突变体的组成。与对照ApoE−/−小鼠相比，巨噬细胞特异性TGF-ß1过表达的动物在WTD（西式饮食）24周后发生动脉粥样硬化的次数明显减少（p<0.05）。动脉粥样硬化病变发展减少与巨噬细胞显著减少相关（WTD 8周和24周后p<0.05），平滑肌细胞(SMCs；WTD治疗24周后p<0.01)，胶原蛋白明显增多（WTD治疗16周和24周后分别p<0.01和p<0.05），但小鼠主动脉弓内膜厚度和巨噬细胞总数无显著差异，提示巨噬细胞特异性TGF-ß1过表达具有稳定斑块的作用。我们的数据显示，巨噬细胞特异性TGF-ß1过表达可减少并稳定apoe缺陷小鼠的动脉粥样硬化斑块。
Although macrophages represent the hallmark of both human and murine atherosclerotic lesions and have been shown to express TGF-ß1 (transforming growth factor β1) and its receptors, it has so far not been experimentally addressed whether the pleiotropic cytokine TGF-ß1 may influence atherogenesis by a macrophage specific mechanism. We developed transgenic mice with macrophage specific TGF-ß1 overexpression, crossed the transgenics to the atherosclerotic ApoE (apolipoprotein E) knock-out strain and quantitatively analyzed both atherosclerotic lesion development and composition of the resulting double mutants. Compared with control ApoE−/− mice, animals with macrophage specific TGF-ß1 overexpression developed significantly less atherosclerosis after 24 weeks on the WTD (Western type diet) as indicated by aortic plaque area en face (p<0.05). Reduced atherosclerotic lesion development was associated with significantly less macrophages (p<0.05 after both 8 and 24 weeks on the WTD), significantly more smooth muscle cells (SMCs; p<0.01 after 24 weeks on the WTD), significantly more collagen (p<0.01 and p<0.05 after 16 and 24 weeks on the WTD, respectively) without significant differences of inner aortic arch intima thickness or the number of total macrophages in the mice pointing to a plaque stabilizing effect of macrophage-specific TGF-ß1 overexpression. Our data shows that macrophage specific TGF-ß1 overexpression reduces and stabilizes atherosclerotic plaques in ApoE-deficient mice.
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影响因子：
4.4
作者：
Petkov, PM;Cassell, MA;Wiles, MV
通讯作者：
Wiles, MV
DOI：
10.1073/pnas.94.9.4642
发表时间：
1997-04-29
影响因子：
11.1
作者：
Dansky, HM;Charlton, SA;Smith, JD
通讯作者：
Smith, JD
鼠腹膜巨噬细胞潜在 TGF-β 激活的表征。
DOI：
--
发表时间：
1995
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Nunes,I;Shapiro,RL;Rifkin,DB
通讯作者：
Rifkin,DB
DOI：
10.1172/jci11380
发表时间：
2001-07
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Li Song;C. Leung;C. Schindler
通讯作者：
Li Song;C. Leung;C. Schindler
影响因子：
20.3
作者：
Shi, Can;Sakuma, Masashi;Simon, Daniel I.
通讯作者：
Simon, Daniel I.