HDL biology
LCAT deficiency posttranscriptionally suppresses plasma CETP levels, likely via loss of HDL (Arterioscler Thromb Vasc Biol 2002)
Original title: Cholesteryl ester transfer protein expressed in lecithin cholesterol acyltransferase-deficient mice
Cross-breeding LCAT-knockout mice with CETP transgenic mice produced 63 offspring classified by LCAT genotype and plasma CETP level (none, low, high). HDL fell as LCAT decreased within each CETP-level group; plasma CETP ranged 0-30 microg/mL in lcat(+/+) and lcat(+/-) mice but stayed under 10 microg/mL in lcat(-/-) mice. In lcat(+/+) and lcat(+/-) mice, rising CETP lowered HDL cholesterol and phospholipid while raising HDL triglyceride and apoB, an effect not detectable in lcat(-/-) mice due to absent mature HDL. CETP genomic DNA and mRNA were similar across genotypes, but the slope linking CETP mRNA to plasma CETP protein was much lower in lcat(-/-) mice, and plasma CETP shifted from mostly HDL-associated in lcat(+/+) mice to free-floating in lcat(-/-) mice, indicating CETP is posttranscriptionally downregulated in LCAT deficiency, likely because extremely low HDL removes its normal carrier.
Original 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 micro g/mL, whereas it was <10 micro 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.