Genetics
Blocking CETP production in liver cells boosts secretion of the smallest, most protective HDL form (Atherosclerosis 1999)
Original title: Secretion of prebeta HDL increases with the suppression of cholesteryl ester transfer protein in Hep G2 cells
Since the role of CETP in hepatic secretion of prebeta HDL, a small protein-rich apoA-I-only lipoprotein, had not been determined, this study suppressed hepatic CETP using liver-targeted antisense oligodeoxynucleotides (ODNs) coupled to asialoglycoprotein carrier molecules in cultured Hep G2 cells, comparing antisense, sense, and saline control groups. Both hepatic CETP mRNA and CETP mass in the medium were significantly lower in the antisense group than sense or control groups (CETP mass 1.697 versus 2.367 and 2.360 ng/mg cell protein). Conversely, hepatic apoA-I mRNA and apoA-I mass in the medium were significantly higher in the antisense group (apoA-I mass 1.877 versus 1.213 and 1.097 microgram/mg cell protein), an increase mainly attributable to prebeta apoA-I. The authors suggest these findings may partly explain the elevated HDL and apoA-I seen in CETP-deficient patients, and indicate that baseline prebeta HDL production may already be sufficient in such patients.
Original abstract
Prebeta HDL are small, protein rich lipoproteins that are predominantly composed of apo A-I, without apo A-II. Prebeta HDL are secreted from the liver as nascent HDL and/or are produced in the incubated plasma by cholesteryl ester transfer protein (CETP). However, the role of CETP in the secretion of HDL from the liver has yet to be determined. In the present study, we examined the effect of the suppression of hepatic CETP by antisense oligodeoxynucleotides (ODNs) against CETP targeted to the liver on the secretion of apo A-I using a Hep G2 cell culture. The ODNs against CETP were coupled to asialoglycoprotein (ASOR) carrier molecules, which serve as an important method for the regulation of liver gene expression. Hep G2 cells were cultured in DMEM supplemented with 10 FBS. After 2 days, the medium was changed to DMEM with EGF and the cells were divided into three groups. The control group received saline, while the sense group was mixed with the sense ODNs complex and the antisense group was mixed with the antisense ODNs complex, respectively, for 2 days. Both the hepatic CETP mRNA and the CETP mass in the medium in the antisense group decreased significantly more than in the sense and the control groups (CETP mass: 1.697 + /- 0.410 ng/mg cell protein vs. 2.367 + /- 0.22 and 2.360 + /- 0.139, n = 3 in each determination). In contrast, both the hepatic apo A-I mRNA and the apo A-I mass in the medium in the antisense group were significantly higher than those in the sense and the control groups (apo A-I mass; 1.877 + /- 0.215 micro/mg cell protein vs. 1.213 + /- 0.282 and 1.097 + /- 0.144, n = 3 in each determination). The increase in apo A-I was mainly due to the increase in prebeta apo A-I. These findings may partly explain why HDL and apo A-I increase in patients with CETP deficiency, while also indicating the possibility that the original level of prebeta HDL is sufficient in such patients.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.