Transgenic rabbits expressing human apolipoprotein(a) develop more extensive atherosclerotic lesions in response to a cholesterol-rich diet
Transgenic rabbits expressing human apolipoprotein(a) develop more extensive atherosclerotic lesions in response to a cholesterol-rich diet
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DOI：
10.1161/01.atv.21.1.88
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发表时间：
2001-01-01
影响因子：
8.7
通讯作者：
Watanabe, T
中科院分区：
文献类型：
--
作者：
Fan, JL;Shimoyamada, H;Watanabe, T
高脂蛋白（a）[Lp（a）]水平是动脉粥样硬化发展的独立危险因素，但Lp（a）与动脉粥样硬化的关系尚不完全清楚。为了检测Lp（a）对动脉粥样硬化发展的影响，我们研究了表达人载脂蛋白（a）[apo（a）]的转基因兔，该转基因兔在血浆中组装成Lp（a）。尽管两组动物血浆中的胆固醇水平相似地升高，但喂食0.3%胆固醇饲料16周的人apo（a）转基因兔子比非转基因兔子有更广泛的动脉粥样硬化病变。与对照组相比，apo（a）转基因兔主动脉、髂动脉和颈动脉的动脉粥样硬化病变面积明显增加。此外，吃高胆固醇食物的转基因兔比对照组的兔有更严重的冠状动脉粥样硬化。免疫组织化学分析显示，人载脂蛋白（a）经常沉积在转基因兔动脉粥样硬化病变。我们的结论是，脂蛋白（a）可能有致动脉粥样硬化的作用，在设置一个高胆固醇的饮食在转基因兔。
High lipoprotein(a) [Lp(a)] levels constitute an independent risk factor for the development of atherosclerosis, However, the relationship between Lp(a) and atherosclerosis is not fully understood. To examine the effect of Lp(a) on the development of atherosclerosis, we studied transgenic rabbits expressing human apolipoprotein(a) [apo(a)], which was assembled into Lp(a) in the plasma. Human apo(a) transgenic rabbits fed a 0.3% cholesterol diet for 16 weeks had more extensive atherosclerotic lesions than did nontransgenic rabbits, although the cholesterol levels in the plasma of both groups were similarly elevated. Compared with the lesions in control rabbits, the areas of the atherosclerotic lesions inhuman apo(a) transgenic rabbits were significantly increased in the aorta, the iliac artery, and the carotid artery. Furthermore, human apo(a) transgenic rabbits on a cholesterol-rich diet had a greater degree of coronary atherosclerosis than did control rabbits. Immunohistochemical analysis revealed that human apo(a) was frequently deposited in the atherosclerotic lesions of transgenic rabbits. We conclude that Lp(a) may have proatherogenic effects in the setting of a cholesterol-rich diet in transgenic rabbits.