Transgenic overexpression of human lecithin: cholesterol acyltransferase (LCAT) in mice does not increase aortic cholesterol deposition

Results from several atherosclerosis studies using morphometric procedures have proven controversial with regard to whether over-expression of human LCAT in transgenic (Tg) mice is atherogenic. The purpose of the present study was to determine the effect of 10-fold over-expression of human LCAT on aortic free and esterified cholesterol (EC) deposition as well as plasma lipoprotein cholesteryl ester (CE) fatty acid composition in mice fed an atherogenic diet containing cholic acid. C57Bl/6 (control) and human LCAT-Tg mice were fed chow or an atherogenic diet (15% of calories from palm oil, 1.0% cholesterol and 0.5% cholic acid) for 24 weeks before measurement of aortic cholesterol content. Compared with the chow diet, control and LCAT-Tg mice fed the atherogenic diet had a 2-fold increase in plasma total, free and EC, a 7-fold increase in plasma apoB lipoprotein cholesterol, and a 40–50-fold increase in hepatic cholesterol content. The aortic EC content was increased in control (0.7 vs. 1.2 mg/g protein) and LCAT-Tg (0.3 vs. 1.5 mg/g protein) mice fed the atherogenic diet compared with those consuming the chow diet; however, there was no difference in aortic free (14.4±6.8 vs. 18.5±7.7 mg/g protein) or esterified (1.2±1.0 vs. 1.5±1.2 mg/g protein) cholesterol content between atherogenic diet-fed control and LCAT-Tg mice, respectively. LCAT-Tg mice fed the atherogenic diet had a 2-fold increase in the ratio of saturated+monounsaturated to polyunsaturated CE species in plasma apoB lipoproteins compared with control mice (9.4±2.4 vs. 4.9±0.7). We conclude that over-expression of human LCAT in Tg mice fed an atherogenic diet containing cholic acid does not result in increased aortic cholesterol deposition compared with control mice, even though the CE fatty acid saturation index of plasma apoB lipoproteins was doubled.