OVEREXPRESSION OF HUMAN LECITHIN CHOLESTERYL ACYLTRANSFERASE IN TRANSGENIC MICE

尽管血浆高密度脂蛋白和载脂蛋白A-I、LCAT浓度升高 转基因(L-TG)小鼠对饮食诱导的动脉粥样硬化有增强作用。在……里面 相比之下，在新西兰兔体内表达相同的转基因会导致 动脉粥样硬化减轻。高密度脂蛋白的主要区别之一是 这两种转基因动物模型之间的代谢是一个缺陷。 胆固醇酯转运蛋白(CETP)在小鼠体内的表达。评估 CETP缺乏是否调节动脉粥样硬化的发展 L-甘油三酯小鼠与L-甘油三酯小鼠杂交。与L-甘油三酯小鼠相比，CETP X L-甘油三酯小鼠降低了血浆胆固醇浓度， 胆固醇酯、高密度脂蛋白胆固醇和载脂蛋白E(-44%、-68%、-49%和-57%) L-TG；p&lt；0.05)。FPLC分析显示富含apoE的细胞明显减少 HDL1。尽管血浆高密度脂蛋白胆固醇浓度下降，但CETP x L-甘油三酯 饮食诱导的动脉粥样硬化(L-TG组的40%； P&lt；0.001)。因此，CETP的表达降低了高密度脂蛋白的异质性，并 L-Tg小鼠体内血药浓度。CETP介导的CE从高密度脂蛋白向 载脂蛋白B可能使L-甘油三酯小鼠高密度脂蛋白组成正常化 和功能，从而减轻LCAT诱导的小鼠动脉粥样硬化。

Despite increased plasma concentrations of HDL and apoA-I, LCAT transgenic (L-Tg) mice have enhance diet-induced atherosclerosis. In contrast, expression of the same transgene in NZW rabbits results in reduced aortic atherosclerosis. One of the major differences in the HDL metabolism between these two transgenic animal models is a deficiency of cholesteryl ester transfer protein (CETP) in mice. To evaluate whether CETP deficiency modulates the development of atherosclerosis in L-Tg mice we crossed CETP-Tg x L-Tg mice. Compared to L-Tg mice, CETP x L-Tg mice had reduced plasma concentrations of cholesterol, cholesteryl esters, HDL-C and apoE (-44%,-68%, -49% and -57% that of L-Tg; p<0.05). FPLC analysis revealed a marked reduction of apoE-rich HDL1. Despite decreased plasma concentrations of HDL-C, CETP x L-Tg mice had reduced diet-induced aortic atherosclerosis (40% that of L-Tg; p<0.001). Thus, CETP expression reduces HDL heterogeneity and concentrations in L-Tg mice. CETP-mediated transfer of CE from HDL to apoB-containing lipoproteins may normalize L-Tg mouse HDL composition and function, thereby reducing LCAT induced atherosclerosis in mice.