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Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1347-1353
Published online before print June 13, 2002, doi: 10.1161/01.ATV.0000026297.50542.62
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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1347.)
© 2002 American Heart Association, Inc.


Atherosclerosis and Lipoproteins

Cholesteryl Ester Transfer Protein Expressed in Lecithin Cholesterol Acyltransferase–Deficient Mice

Cheng-ai Wu; Maki Tsujita; Kuniko Okumura-Noji; Shinichi Usui; Hajime Kakuuchi; Mitsuyo Okazaki; Shinji Yokoyama

From Biochemistry, Cell Biology, and Metabolism (C.W., M.T., K.O.-N., S.Y.), Nagoya City University Graduate School of Medical Science, Nagoya; Biochemistry and Biophysics, Graduate School of Allied Health Sciences (S.U.), Tokyo Medical and Dental University, Tokyo; and Laboratory of Chemistry (H.K., M.O.), College of Liberal Arts and Science, Tokyo Medical and Dental University, Ichikawa, Japan.

Correspondence to Shinji Yokoyama, MD, PhD, FRCPC, Biochemistry, Cell Biology, and Metabolism, Nagoya City University Graduate School of Medical Science, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. E-mail syokoyam{at}med-nagoya-cu.ac.jp

Objective— Regulation of plasma cholesteryl ester transfer protein (CETP) concentration was studied in lecithin-cholesterol acyltransferase (LCAT)-knockout mice.

Methods and Results— LCAT-knockout mice were cross-bred with CETP transgenic mice. The offspring (n=63) were classified for LCAT genotype and plasma CETP levels (no CETP, low CETP, and high CETP). High density lipoprotein (HDL) decreased as LCAT decreased in each CETP-level group. In the lcat(+/+) and lcat(+/-) mice, plasma CETP varied from 0 to 30 µg/mL, whereas it was <10 µg/mL in the lcat(-/-) mice. HDL cholesterol and phospholipid decreased and HDL triglyceride and apolipoprotein B increased in CETP in the lcat(+/+) and lcat(+/-) mice, whereas there was no difference in HDL between low and high CETP. An effect of CETP on HDL was not detected in the lcat(-/-) mice because of the absence of mature HDL. Genomic DNA and mRNA of CETP were correlated and were similar in the lcat(-/-) and lcat(+/+) mice. Plasma CETP was correlated with its genomic DNA and mRNA, but the slope of the increase was much lower in the lcat(-/-) mice. Whereas plasma CETP mostly associates with HDL in the lcat(+/+) mouse, it is found free in the lcat(-/-) mouse.

Conclusions— Plasma CETP is posttranscriptionally downregulated in the lcat(-/-) mice, presumably by its extremely low HDL.


Key Words: cholesterol • high density lipoprotein • lecithin-cholesterol acyltransferase • cholesteryl ester transfer protein • mice




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M. Tsujita, C.-A. Wu, S. Abe-Dohmae, S. Usui, M. Okazaki, and S. Yokoyama
On the hepatic mechanism of HDL assembly by the ABCA1/apoA-I pathway
J. Lipid Res., January 1, 2005; 46(1): 154 - 162.
[Abstract] [Full Text] [PDF]