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

Abstract

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 &mgr;g/mL, whereas it was <10 &mgr;g/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.