Effect of CETP on the plasma lipoprotein profile in four strains of transgenic mouse.
The plasma cholesteryl ester transfer protein (CETP) plays a central role in high-density lipoprotein (HDL) metabolism and reverse cholesterol transport. There are conflicting views regarding whether or not excessive CETP activity is one of the risk factors of atherosclerosis. To study how much effect CETP can have on the profiles of plasma lipoproteins in vivo, we produced four strains of transgenic mouse that expressed different levels of human CETP gene. We analyzed seven groups of mice that had different levels of CETP expression. The cholesterol level of HDL, chylomicron (CM) and VLDL, intermediate density lipoprotein (IDL) and LDL were proportionally changed in association with plasma CETP concentrations (2.9 +/- 0.6 to 37.4 +/- 1.7 microg/ml) in an allelic dose-dependent manner. We further characterized one of the transgenic strains, CETP-4, by optimizing the experimental condition for the mouse model of atherosclerosis, and found that it would be useful for the development of therapeutics against atherosclerosis.
Takahashi
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Pharmaceutical Frontier Research Laboratories, Central Pharmaceutical Research Institute, JT Inc., 13-2, Fukuura 1-chome, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan. hikaru.takahashi@ims.jti.co.jp
Takahashi
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A
Maki
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Sasai
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Kamada
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D000818:Animals; D001011:Aorta / Q000473:pathology; D001161:Arteriosclerosis / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000097:blood / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D002914:Chylomicrons / Q000097:blood; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D015870:Gene Expression; D006023:Glycoproteins; D006579:Heterozygote; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000097:blood*; D019683:Penetrance
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D002914:Chylomicrons; D006023:Glycoproteins; D008074:Lipoproteins; C030104:lipoprotein cholesterol; D002784:Cholesterol