OVEREXPRESSION OF HUMAN LECITHIN CHOLESTERYL ACYLTRANSFERASE IN TRANSGENIC MICE

为了评价LCAT在高密度脂蛋白代谢中的作用，以及 小鼠的血浆水平是对照组(1微克/毫升)的100倍。相比较 在24名年龄和性别匹配的兄弟姐妹中，转基因小鼠的血浆水平升高 TC(占NL的133-237%)、CE(占NL的141-267%)和HDL-C(占NL的123-209%)，但 相似的血浆甘油三酯，含磷脂，含B的脂蛋白水平， 载脂蛋白A-I和载脂蛋白A-II。HLCAT TG血浆的FPLC分析显示 大小的高密度脂蛋白颗粒富含CE和PL。因此，LCAT调节 老鼠。 LCAT在调节饮食反应中的潜在作用。节食前 对照组血脂水平(mg/dl)为TC=97+/-11，HDL72+/-10。 饮食后血脂水平 对照组为TC=290+/-55，高密度脂蛋白=85+/-15，而转基因组为 TC=313+/-83，高密度脂蛋白=115+/-27。因此，在HF饮食中，转基因小鼠有 显著提高(p&lt；0.05)高密度脂蛋白胆固醇以及降低总胆固醇/高密度脂蛋白比率 与对照组相比，TG、PL、CE、LCAT质量和 活动。转基因小鼠血浆的FPLC分析显示 高密度脂蛋白胆固醇、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇升高，低密度脂蛋白/低密度脂蛋白胆固醇降低， CE和PL，显示LCAT介导的血脂调节 对饮食挑战的回应。 为了评价过表达人LCAT基因的效果 关于饮食诱导的动脉粥样硬化控制(N=19)和LCAT转基因(N=18) 在开始高脂饮食16周后，对C57BL小鼠进行分析。 对照和转基因小鼠。这些发现表明，在这种动物中 CETP缺乏模型，LCAT过度表达不能保护 抗饮食诱导的动脉粥样硬化的发展。

In order to evaluate the role of LCAT in HDL metabolism, and atherosclerosis we have generated transgenic mice overexpressing hLCAT at plasma levels 100 fold higher than control (1 ug/ml) mice. Compared to 24 age and sex-matched siblings, transgenic mice had elevated plasma TC (133-237% of NL), CE (141-267% of NL) and HDL-C (123-209% of NL) but similar plasma levels of triglycerides, PL, B-containing lipoproteins, apoA-I and apoA-II. FPLC analysis of hLCAT TG plasma revealed larger sized HDL particles enriched in CE and PL. Thus, LCAT modulates the composition and heterogeneity as well as the concentrations of HDL in mice. Age/sex matched transgenic (M=7, F=8) and control (M=14, F=13) animals were then placed on a high chol-fat (HF) diet for 21 d to investigate the potential role of LCAT in modulating dietary responses. Pre-diet lipid values (mg/dl) in controls were TC=97+/-11, HDL=72+/-10 and in transgenics were TC=121 +/-16, HDL-C=84 +/-17. Post-diet lipid values in controls were TC=290+/-55, HDL= 85+/-15, and in transgenics were TC=313+/-83, HDL=115+/-27. Thus, on the HF diet transgenic mice had significantly higher (p<0.05) HDL-C as well as reduced TC/HDL ratios than controls, without differences in Tg, PL, CE, LCAT mass and activity. FPLC analysis of transgenic mouse plasma revealed significant increases in HDL-C, CE and PL with reciprocal decreases in IDL/LDL-C, CE and PL, demonstrating LCAT-mediated modulation of plasma lipids in response to a dietary challenge. In order to evaluate the effect of overexpressing the human LCAT gene on diet-induced atherosclerosis control (N=19)and LCAT transgenic (N=18) C57Bl mice were analyzed 16 weeks after initiation of a high fat-diet. Analysis of mean aortic lesion size revealed no differences between control and transgenic mice. These findings indicate that in this animal model with a deficiency of CETP, LCAT overexpression does not protect against the development of diet-induced atherosclerosis.