DECREASED EARLY ATHEROSCLEROTIC LESIONS IN HYPERTRIGLYCERIDEMIC MICE EXPRESSING CHOLESTERYL ESTER TRANSFER PROTEIN TRANSGENE
DECREASED EARLY ATHEROSCLEROTIC LESIONS IN HYPERTRIGLYCERIDEMIC MICE EXPRESSING CHOLESTERYL ESTER TRANSFER PROTEIN TRANSGENE
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DOI：
10.1172/jci118255
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发表时间：
1995-10-01
影响因子：
15.9
通讯作者：
TALL, AR
中科院分区：
文献类型：
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作者：
HAYEK, T;MASUCCIMAGOULAS, L;TALL, AR
人胆固醇酯转移蛋白（CETP）促进胆固醇酯从HDL转移到富含胆固醇的脂蛋白。CETP的活性导致HDL胆固醇水平降低，但CETP也可能促进胆固醇逆向转运。因此，CETP表达对动脉粥样硬化形成的净影响是不确定的。通过给转基因小鼠喂食高胆固醇饲料16周，评估高脂血症和CETP对近端主动脉粥样硬化病变发展的影响。14只高脂血症人载脂蛋白C Ⅲ（HuC Ⅲ）转基因（Tg）小鼠中有13只（93%）出现动脉粥样硬化病变，而29只对照小鼠中有18只（62%）出现动脉粥样硬化病变。在HuCIII/CETPTg、人apo AI/CIITTg和HuAI/CIII/CETPTg小鼠中，分别有7/13只（54%）、5/10只（50%）和5/13只（38%）在近端主动脉中出现病变（与HuCIIITg相比，P <0.05）。HuCIIITg和对照组每只小鼠的平均主动脉病变数量分别为3.4+/-0.8和2.7+/-0.6; HuCIII/CETPTg、HuAI/CIIITg和HuAI/CIII/CETPTg小鼠的病变数量显著低于HuCIIITg和对照组小鼠：分别为0.9+/-0.4、1.5 +/-0.5和0.9+/-0.4。平均病变面积平行减少。在另一项研究中，我们发现非高脂血症CETP转基因小鼠与对照组相比，对饮食性动脉粥样硬化的易感性增加。我们的结论是CETP表达抑制早期动脉粥样硬化病变的发展，但仅在高脂血症小鼠。
The human cholesteryl ester transfer protein(CETP) facilitates the transfer of cholesteryl ester from HDL to triglyceride-rich lipoproteins. The activity of CETP results in a reduction in HDL cholesterol levels, but CETP may also promote reverse cholesterol transport. Thus, the net impact of CETP expression on atherogenesis is uncertain. The influence of hypertriglyceridemia and CETP on the development of atherosclerotic lesions in the proximal aorta was assessed by feeding transgenic mice a high cholesterol diet for 16 wk, 13 out of 14 (93%) hypertriglyceridemic human apo CIII (HuCIII) transgenic (Tg) mice developed atherosclerotic lesions, compared to 18 out of 29 (62%) controls. In HuCIII/CETPTg, human apo AI/CIITTg and HuAI/CIII/CETPTg mice, 7 of 13 (54%), 5 of 10 (50%), and 5 of 13 (38%), respectively, developed lesions in the proximal aorta (P < .05 compared to HuCIIITg). The average number of aortic lesions per mouse in HuCIIITg and controls was 3.4+/-0.8 and 2.7+/-0,6, respectively; in HuCIII/CETPTg, HuAI/CIIITg, and HuAI/CIII/CETPTg mice, the number of lesions was significantly lower than in HuCIIITg and control mice: 0.9+/-0.4, 1.5+/-0.5, and 0.9+/-0.4, respectively. There were parallel reductions in mean lesion area. In a separate study, we found an increased susceptibility to dietary atherosclerosis in nonhypertriglyceridemic CETP transgenic mice compared to controls. We conclude that CETP expression inhibits the development of early atherosclerotic lesions but only in hypertriglyceridemic mice.