Overexpression of lipoprotein lipase in transgenic rabbits leads to increased small dense LDL in plasma and promotes atherosclerosis
Overexpression of lipoprotein lipase in transgenic rabbits leads to increased small dense LDL in plasma and promotes atherosclerosis
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DOI：
10.1038/labinvest.3700102
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发表时间：
2004-06-01
影响因子：
5
通讯作者：
Fan, JL
中科院分区：
文献类型：
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作者：
Ichikawa, T;Kitajima, S;Fan, JL
脂蛋白脂酶(LPL)是富含甘油三酯的脂蛋白的水解酶。之前使用转基因小鼠和兔子进行的研究已经证明，脂肪和骨骼肌中高水平的LPL活性可以预防饮食诱导的高胆固醇血症，从而防止主动脉粥样硬化。然而，LPL活性的增加本身是否具有抗动脉粥样硬化作用，或者LPL的抗动脉粥样硬化作用是否依赖于LPL的降脂作用，这一点本身尚不清楚。为了解决这个问题，我们给转基因和产仔兔饲喂含有不同量胆固醇(0.3-0.6%)的饲料，以将它们的血浆胆固醇浓度维持在类似的高水平16周。我们分析了他们的脂蛋白图谱，并比较了他们对动脉粥样硬化的易感性。结果表明，转基因兔体内LPL的过表达降低了残余脂蛋白(β-VLDL，d
Lipoprotein lipase (LPL) is a key enzyme in the hydrolysis of triglyceride-rich lipoproteins. Previous studies using transgenic mice and rabbits have demonstrated that high level of LPL activity in adipose and skeletal muscle protects against diet-induced hypercholesterolemia and subsequently prevents aortic atherosclerosis. However, it is unknown, per se, whether increased LPL activity itself is antiatherogenic, or whether the antiatherogenic effect of LPL is dependent upon the LPL lipid-lowering effect. To address this issue, we fed LPL transgenic and littermate rabbits diets containing different amounts of cholesterol (0.3-0.6%) adjusted to maintain their plasma cholesterol concentrations at similarly high levels for 16 weeks. We analyzed their lipoprotein profiles and compared their susceptibility to atherosclerosis. The results showed that the overexpression of LPL in transgenic rabbits reduced remnant lipoproteins (beta-VLDL, d