CETP is a determinant of serum LDL-cholesterol but not HDL-cholesterol in healthy Japanese

Kinoshita, Makoto; Teramoto, Tamio; Shimazu, Nobuko; Kaneko, Kazuko; Ohta, Miki; Koike, Toru; Hosogaya, Shigemi; Kume, Shoko; Yamanaka, Masami

doi:10.1016/0021-9150(95)05684-x

Cited by 29 publications

(14 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Values are the mean Ϯ S.E. *, p Ͻ 0.05. homozygotes for CETP deficiency, which showed almost no CETP levels, demonstrated markedly elevated HDL-C and plasma apoA-I levels (3,4), wide-ranged CETP levels showed no significant correlation to HDL cholesterol in healthy Japanese (27) and normotriglyceridemic man (28). In our study, since the CETP is from low to high levels in the four groups, it might be speculated that the reduction of CETP affected HDL cholesterol little.…”

Section: Discussionmentioning

confidence: 80%

Effect of Antisense Oligonucleotides against Cholesteryl Ester Transfer Protein on the Development of Atherosclerosis in Cholesterol-fed Rabbits

Shinoda¹,

Makino²,

Sawada³

et al. 1998

Journal of Biological Chemistry

233

140

View full text Add to dashboard Cite

Cholesteryl ester transfer protein (CETP) is the enzyme that facilitates the transfer of cholesteryl ester from high density lipoprotein (HDL) to apolipoprotein B (apoB)-containing lipoproteins. However, the exact role of CETP in the development of atherosclerosis has not been determined. In the present study, we examined the effect of the suppression of increased plasma CETP by intravenous injection with antisense oligodeoxynucleotides (ODNs) against CETP targeted to the liver on the development of atherosclerosis in rabbits fed a cholesterol diet. The ODNs against rabbit CETP were coupled to asialoglycoprotein (ASOR) carrier molecules, which serve as an important method to regulate liver gene expression. Twenty-two male Japanese White rabbits were used in the experiment. Eighteen animals were fed a standard rabbit chow supplemented with 0.3% cholesterol throughout the experiment for 16 weeks. At 8 weeks, they were divided into three groups (six animals in each group), among which the plasma total and HDL cholesterol concentrations did not significantly change. The control group received nothing, the sense group were injected with the sense ODNs complex, and the antisense group were injected with the antisense ODNs complex, respectively, for subsequent 8 weeks. ASOR⅐poly(L-lysine) ODNs complex were injected via the ear veins twice a week. Four animals were fed a standard rabbit diet for 16 weeks. The total cholesterol concentrations and the CETP mass in the animals injected with antisense ODNs were all significantly decreased in 12 and 16 weeks compared with those injected with sense ODNs and the control animals. The HDL cholesterol concentrations measured by the precipitation assay did not significantly change among the groups fed a cholesterol diet, and triglyceride concentrations did not significantly change in the four groups. However, at the end of the study, when the HDL cholesterol concentrations were measured after the isolation by ultracentrifugation and a column chromotography, they were significantly higher in the animals injected with antisense ODNs than in the animals injected with sense ODNs and in the control animals. A reduction of CETP mRNA and an increase of LDL receptor mRNA in the liver were observed in the animals injected with antisense ODNs compared with those injected with sense ODNs and the control animals. Aortic cholesterol contents and the aortic percentage lesion to total surface area were significantly lower in the animals injected with antisense ODNs than in the animals injected with sense ODNs and in the control animals. These findings showed for the first time that suppression of increased plasma CETP by the injection with antisense ODNs against CETP coupled to ASOR carrier molecules targeted to the liver could thus inhibit the atherosclerosis possibly by decreasing the plasma LDL ؉ very low density lipoprotein (VLDL) cholesterol in cholesterol-fed rabbits. Cholesteryl ester transfer protein (CETP)1 is a plasma glycoprotein that catalyzes the transfer of cholesteryl ester and tr...

show abstract

Section: Discussionmentioning

confidence: 80%

Effect of Antisense Oligonucleotides against Cholesteryl Ester Transfer Protein on the Development of Atherosclerosis in Cholesterol-fed Rabbits

Shinoda¹,

Makino²,

Sawada³

et al. 1998

Journal of Biological Chemistry

233

140

View full text Add to dashboard Cite

show abstract

“…Therefore, the higher BMI in female compared with male diabetic subjects does not explain their higher plasma CETP concentration. Since other reports also showed slightly higher plasma CETP levels in female subjects (32,33), a sex effect, as such, is possible. However in the diabetic group, this sex effect on plasma CETP did not result in a significant difference in plasma CET between male and female sub- jects.…”

Section: Discussionmentioning

confidence: 81%

Plasma Cholesteryl Ester Transfer Is a Determinant of Intima-Media Thickness in Type 2 Diabetic and Nondiabetic Subjects

et al. 2005

View full text Add to dashboard Cite

We tested whether carotid artery intima-media thickness (IMT) is associated with plasma cholesteryl ester transfer (CET) and/or the plasma cholesteryl ester transfer protein (CETP) concentration in type 2 diabetic and control subjects. In 87 male and female subjects with type 2 diabetes (nonsmokers, no insulin or lipid-lowering drug treatment) and 82 control subjects, IMT, plasma CET, CETP mass, and lipids were determined. HDL cholesterol was lower, whereas IMT, pulse pressure, plasma triglycerides, and plasma CET and CETP concentration were higher in diabetic patients versus control subjects. In diabetic patients, plasma CET was positively determined by triglycerides (P < 0.001), non-HDL cholesterol (P < 0.001), CETP (P ‫؍‬ 0.002), and the interaction between CETP and triglycerides (P ‫؍‬ 0.004). In control subjects, plasma CET was positively related to triglycerides (P < 0.001) and non-HDL cholesterol (P < 0.001). HDL cholesterol was inversely related to plasma CET in each group (P < 0.01 for both). IMT was positively associated with plasma CET in diabetic (P ‫؍‬ 0.05) and control (P < 0.05) subjects after adjustment for age, sex, and pulse pressure. No independent relationship with plasma CETP mass was found. Plasma CET is a positive determinant of IMT. Plasma CETP mass, in turn, is a determinant of CET with an increasing effect at higher triglycerides. These data, therefore, provide a rationale to evaluate the effects of CETP inhibitor treatment on plasma CET and on cardiovascular risk in diabetes-associated hypertriglyceridemia. Diabetes 54:3554 -3559, 2005 T he inverse relationship between HDL cholesterol and cardiovascular disease is well documented in nondiabetic and type 2 diabetic populations (1,2). Among other mechanisms, the cholesteryl ester transfer protein (CETP)-mediated process of plasma CET plays a key role in HDL metabolism. CETP transfers cholesteryl esters from HDL toward lipoproteins of lowerdensity classes in exchange for triglycerides (3-5). Hence, the plasma CET process is likely to contribute to low HDL cholesterol, as frequently observed in type 2 diabetes (5).Only few studies have addressed the effect of plasma CETP levels and the rate of plasma CET on cardiovascular risk in humans. A small study showed a positive correlation between the plasma CETP concentration and carotid artery intima-media thickness (IMT) (6). In addition, plasma CETP mass was shown to be a positive determinant of incident coronary artery disease but only in subjects with high triglycerides (7). The CET process itself could, however, also represent a beneficial pathway by enabling the transport of HDL-derived cholesteryl esters back to the liver via VLDL and LDL (3). The impact of the plasma CET process on atherosclerosis development remains, therefore, uncertain (8).CETP inhibitors represent a new class of drugs that effectively raise HDL cholesterol (9,10). While pharmacological inhibition of circulating CETP has been shown to retard atherosclerosis in animal experiments (11), the effect of this treatment on ca...

show abstract

“…A clinical trial using CETP inhibitor has failed to show the protective effect for CHD, although participants in this study showed an extremely HDL-C elevation almost equivalent to very high HDL-C level in our study 30) . Some previous studies have shown mild inverse or no association between HDL-C concentrations and plasma CETP activity [31][32][33] . Moreover, plasma CETP activity showed inverse correlation with CVD risk independent of HDL-C levels 34) .…”

Section: Resultsmentioning

confidence: 92%

The Relationship between Very High Levels of Serum High-Density Lipoprotein Cholesterol and Cause-Specific Mortality in a 20-Year Follow-Up Study of Japanese General Population

Hirata

Okamura

Sugiyama

et al. 2016

J Atheroscler Thromb

View full text Add to dashboard Cite

CETP is a determinant of serum LDL-cholesterol but not HDL-cholesterol in healthy Japanese

Cited by 29 publications

References 28 publications

Effect of Antisense Oligonucleotides against Cholesteryl Ester Transfer Protein on the Development of Atherosclerosis in Cholesterol-fed Rabbits

Effect of Antisense Oligonucleotides against Cholesteryl Ester Transfer Protein on the Development of Atherosclerosis in Cholesterol-fed Rabbits

Plasma Cholesteryl Ester Transfer Is a Determinant of Intima-Media Thickness in Type 2 Diabetic and Nondiabetic Subjects

The Relationship between Very High Levels of Serum High-Density Lipoprotein Cholesterol and Cause-Specific Mortality in a 20-Year Follow-Up Study of Japanese General Population

Contact Info

Product

Resources

About