Overexpression of human lecithin:cholesterol acyltransferase in mice offers no protection against diet‐induced atherosclerosis Note

Human lecithin:cholesterol acyltransferase (LCAT) is a key enzyme in the metabolism of cholesterol. We have used homozygous transgenic mice overexpressing the human LCAT transgene to study the effect of a “Western‐type” atherogenic diet (30% fat, 5% cholesterol and 2% cholic acid) on their LCAT expression, activity, lipoprotein profile and tendency to develop atherosclerosis. The LCAT activity was 35‐fold higher in serum of the homozygous transgenic mice than in murine control serum, and decreased 11–20% in the transgenic mice when fed the atherogenic diet. The total cholesterol and high‐density lipoprotein cholesterol (HDL‐C) concentrations were approximately doubled in the transgenic mice compared with the controls when both groups were fed a regular chow diet. In mice on the atherogenic diet, the triglyceride concentration decreased about 50% to the same level in transgenic and control mice. Total cholesterol and HDL‐C concentrations increased and were 60–80% higher in the transgenic mice. The expression of LCAT mRNA in the liver was decreased by 49–60% in the transgenic mice when fed the atherogenic diet. The development of atherosclerosis was similar in transgenic and control mice. Thus, the 14‐ to 27‐fold higher LCAT activity and the higher HDL‐C concentrations in the homozygous LCAT transgenic mice had no significant protective influence on the development of diet‐induced atherosclerosis.