on June 13, 2002
Published online before print June 13, 2002, doi: 10.1161/01.ATV.0000026297.50542.62
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Submitted on March 6, 2002
Accepted on May 28, 2002
Cholesteryl Ester Transfer Protein Expressed in Lecithin. Cholesterol Acyltransferase--Deficient Mice
Cheng-ai Wu ;
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.
* To whom correspondence should be addressed. 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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