Macrophage-derived lipoprotein lipase increases aortic atherosclerosis in cholesterol-fed Tg rabbits
Macrophage-derived lipoprotein lipase increases aortic atherosclerosis in cholesterol-fed Tg rabbits
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DOI：
10.1016/j.atherosclerosis.2004.10.044
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发表时间：
2005-03-01
期刊：
影响因子：
5.3
通讯作者：
Fan, JL
中科院分区：
文献类型：
--
作者：
Ichikawa, T;Liang, JY;Fan, JL
巨噬细胞产生的脂蛋白脂酶（LPL）在动脉粥样硬化病变中上调;然而，巨噬细胞衍生的LPL增加是否促动脉粥样硬化尚不完全清楚。为了检验动脉壁中巨噬细胞来源的LPL增强动脉粥样硬化病变形成的假设，我们产生了在人清道夫受体增强子/启动子的控制下表达人LPL转基因的转基因（Tg）兔，其驱动人LPL基因的巨噬细胞特异性表达。我们喂养Tg和非Tg同窝出生的兔子的饮食含有0.3%的胆固醇16周，并比较他们的脂蛋白和主动脉粥样硬化。我们发现，Tg和非Tg兔之间的血脂或脂蛋白谱没有差异，但是，动脉粥样硬化病变显着增加Tg相比，非Tg兔。通过图像分析系统评估，主动脉面内病变增加了1.4倍，内膜病变增加了2倍。此外，免疫组化染色显示，增加动脉粥样硬化病变存在于Tg兔的特点是显着积累的巨噬细胞衍生的泡沫细胞，并经常与氧化LDL的沉积。这些结果支持了动脉壁中巨噬细胞源性LPL是促动脉粥样硬化的，可能是通过在动脉粥样硬化形成过程中增强泡沫细胞形成。(c)2004爱思唯尔爱尔兰有限公司保留所有权利。
Lipoprotein lipase (LPL) produced by macrophages is upregulated in the atherosclerotic lesions; however, it is not fully understood whether increased macrophage-derived LPL is pro-atherogenic. To examine the hypothesis that macrophage-derived LPL in the arterial wall enhances atherosclerotic lesion formation, we generated transgenic (Tg) rabbits that express the human LPL transgene under the control of the human scavenger receptor enhancer/promoter, which drives macrophage-specific expression of the human LPL gene. We fed Tg and non-Tg littermate rabbits a diet containing 0.3% cholesterol for 16 weeks and compared their lipoproteins and aortic atherosclerosis. We found that there was no difference in plasma lipid or lipoprotein profiles between Tg and non-Tg rabbits; however, atherosclerotic lesions were significantly increased in Tg compared to non-Tg rabbits. There was a 1.4-fold increase in total aortic en face lesions and a 2-fold increase in intimal lesions evaluated by image analysis system. Furthermore, immunohistochemical staining revealed that the increased atherosclerotic lesions present in Tg rabbits were characterized by marked accumulation of macrophage-derived foam cells and frequently associated with the deposition of oxidized LDL. These results support the notion that macrophage-derived LPL in the arterial wall is pro-atherogenic, possibly via the enhancement of foam cell formation during atherogenesis. (c) 2004 Elsevier Ireland Ltd. All rights reserved.