Mice overexpressing human lecithin: cholesterol acyltransferase are not protected against diet-induced atherosclerosis.
Lecithin: cholesterol acyltransferase (LCAT) (EC 2.3.1.43) is generally assumed to participate in reverse cholesterol transport, i.e., cholesterol transport from peripheral tissues to the liver. LCAT is secreted by the liver and transported in plasma mostly associated with high density lipoprotein. It catalyzes the esterification of cholesterol, mainly high density lipoprotein cholesterol, and produces cholesteryl ester and lysolecithin. Transgenic mice overexpression human LCAT on a C57BL/6 background have elevated high density lipoprotein cholesterol and markedly reduced low and very low density lipoprotein cholesterol and triglyceride levels in plasma, suggesting that such mice may be less susceptible to diet-induced atherosclerosis than isogenic nontransgenic controls. To determine if the apparent anti-atherogenic lipoprotein profile of the LCAT transgenics reduced their susceptibility to atherogenesis, the atherosclerotic lesions developing in transgenic LCAT mice and controls when fed an atherogenic diet were compared by histology and morphometry. Histological examination of the aortas from mice fed a high fat diet for 12, 17 and 22 weeks revealed that the aortic lesions were no smaller or less developed in the transgenic LCAT mice than in the C57BL/6 controls. After 17 weeks there were significantly more "fatty streaks" in the transgenic mice than in the controls. Thus, overexpression of human LCAT in transgenic mice, in spite of their very favourable blood lipoprotein and lipid profile, does not protect against development of atherosclerosis.
Mehlum
A
A
Biotechnology Centre of Oslo, University of Oslo, Norway.
Muri
M
M
Hagve
T A
TA
Solberg
L A
LA
Prydz
H
H
D000818:Animals; D001011:Aorta / Q000473:pathology; D001161:Arteriosclerosis / Q000201:enzymology* / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D004036:Diet, Atherogenic; D008074:Lipoproteins / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood
D008074:Lipoproteins; D014280:Triglycerides; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase