Cholesteryl-ester transfer protein enhances the ability of high-density lipoprotein to inhibit low-density lipoprotein oxidation

IUBMB Life ◽  
2011 ◽  
pp. n/a-n/a ◽  
Author(s):  
David Hine ◽  
Bharti Mackness ◽  
Mike Mackness
Keyword(s):  
High Density Lipoprotein ◽  
Cholesteryl Ester ◽  
Cholesteryl Ester Transfer Protein ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Low Density ◽  
Lipoprotein Oxidation ◽  
Transfer Protein ◽  
Low Density Lipoprotein Oxidation

scholarly journals Bexarotene Induces Dyslipidemia by Increased Very Low-Density Lipoprotein Production and Cholesteryl Ester Transfer Protein-Mediated Reduction of High-Density Lipoprotein

Endocrinology ◽  
2009 ◽  
Vol 150 (5) ◽  
pp. 2368-2375 ◽  
Author(s):  
Jitske de Vries-van der Weij ◽  
Willeke de Haan ◽  
Lihui Hu ◽  
Maarten Kuif ◽  
H. Ling D. W. Oei ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
High Density Lipoprotein ◽  
Cholesteryl Ester ◽  
Cholesteryl Ester Transfer Protein ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Differentiated Thyroid Carcinoma ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Transfer Protein

A common dose-limiting side effect of treatment with the retinoid X receptor agonist bexarotene is dyslipidemia. We evaluated the effects of bexarotene on plasma lipid metabolism in patients with metastatic differentiated thyroid carcinoma and investigated the underlying mechanism(s) in apolipoprotein (APO) E*3-Leiden mice without (E3L) and with human cholesteryl ester transfer protein (CETP; E3L.CETP). To this end, 10 patients with metastatic differentiated thyroid carcinoma were treated with bexarotene (300 mg/d) for 6 wk. Bexarotene increased plasma triglyceride (TG; +150%), primarily associated with very low-density lipoprotein (VLDL), and raised plasma total cholesterol (+50%). However, whereas bexarotene increased VLDL-cholesterol (C) and low-density lipoprotein (LDL)-C (+63%), it decreased high-density lipoprotein (HDL)-C (−30%) and tended to decrease apoAI (−18%) concomitant with an increase in endogenous CETP activity (+44%). To evaluate the cause of the bexarotene-induced hypertriglyceridemia and the role of CETP in the bexarotene-induced shift in cholesterol distribution, E3L and E3L.CETP mice were treated with bexarotene through dietary supplementation [0.03% (wt/wt)]. Bexarotene increased VLDL-associated TG in both E3L (+47%) and E3L.CETP (+29%) mice by increasing VLDL-TG production (+68%). Bexarotene did not affect the total cholesterol levels or distribution in E3L mice but increased VLDL-C (+11%) and decreased HDL-C (−56%) as well as apoAI (−31%) in E3L.CETP mice, concomitant with increased endogenous CETP activity (+41%). This increased CETP activity by bexarotene-treatment is likely due to the increase in VLDL-TG, a CETP substrate that drives CETP activity. In conclusion, bexarotene causes combined dyslipidemia as reflected by increased TG, VLDL-C, and LDL-C and decreased HDL-C, which is the result of an increased VLDL-TG production that causes an increase of the endogenous CETP activity.

scholarly journals Is high-density lipoprotein a modifiable treatment target or just a biomarker for cardiovascular disease?

2019 ◽  
Vol 8 ◽  
pp. 204800401986973 ◽  
Author(s):  
Martin B Whyte
Keyword(s):  
High Density Lipoprotein ◽  
Cholesteryl Ester ◽  
High Density Lipoprotein Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Cholesterol Concentration ◽  
Low Density ◽  
Transfer Protein

Epidemiological data strongly support the inverse association between high-density lipoprotein cholesterol concentration and cardiovascular risk. Over the last three decades, pharmaceutical strategies have been partially successful in raising high-density lipoprotein cholesterol concentration, but clinical outcomes have been disappointing. A recent therapeutic class is the cholesteryl ester transfer protein inhibitor. These drugs can increase circulating high-density lipoprotein cholesterol levels by inhibiting the exchange of cholesteryl ester from high-density lipoprotein for triacylglycerol in larger lipoproteins, such as very low-density lipoprotein and low-density lipoprotein. Recent trials of these agents have not shown clinical benefit. This article will review the evidence for cardiovascular risk associated with high-density lipoprotein cholesterol and discuss the implications of the trial data for cholesteryl ester transfer protein inhibitors.

scholarly journals Pistachio Intake Increases High Density Lipoprotein Levels and Inhibits Low-Density Lipoprotein Oxidation in Rats

2007 ◽  
Vol 212 (1) ◽  
pp. 43-48 ◽  
Author(s):  
Nur Aksoy ◽  
Mehmet Aksoy ◽  
Cahit Bagci ◽  
H. Serdar Gergerlioglu ◽  
Hakim Celik ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Low Density ◽  
Lipoprotein Oxidation ◽  
Low Density Lipoprotein Oxidation
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