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

Abstract

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.

• Authors: A Mehlum, E Gjernes, L A Solberg, T A Hagve, H Prydz
• Journal: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica (APMIS) Vol. 108 Issue 5 Pg. 336-42 (May 2000) ISSN: 0903-4641 [Print] Denmark
• PMID: 10937770 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cholesterol, HDL
• Phosphatidylcholine-Sterol O-Acyltransferase

Topics

• Animals
• Aorta (pathology)
• Arteriosclerosis (prevention & control)
• Cholesterol, HDL (blood)
• Diet
• Female
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Phosphatidylcholine-Sterol O-Acyltransferase (genetics, physiology)