Overexpression of human lecithin:cholesterol acyltransferase in mice offers no protection against diet-induced atherosclerosis.
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.
Biotechnology Centre of Oslo, University of Oslo and the Department of Comparative Medicine, National Hospital, Norway.
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A
Mehlum
E
E
Gjernes
L A
LA
Solberg
T A
TA
Hagve
H
H
Prydz
D000818:Animals; D001011:Aorta / Q000473:pathology; D001161:Arteriosclerosis / Q000517:prevention & control*; D008076:Cholesterol, HDL / Q000097:blood; D004032:Diet; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics / Q000502:physiology*
D008076:Cholesterol, HDL; D007862:Phosphatidylcholine-Sterol O-Acyltransferase