Atherosclerosis and Lipoproteins |
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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