التفاصيل البيبلوغرافية
| العنوان: |
Effects of the cholesteryl ester transfer protein inhibitor, TA-8995, on cholesterol efflux capacity and high-density lipoprotein particle subclasses. |
| المؤلفون: |
van Capelleveen, Julian C., Kastelein, John J.P., Zwinderman, Aeilko H., van Deventer, Sander J.H., Collins, Heidi L., Adelman, Steven J., Round, Patrick, Ford, John, Rader, Daniel J., Hovingh, G. Kees |
| المصدر: |
Journal of Clinical Lipidology; Sep2016, Vol. 10 Issue 5, p1137-1144.e3, 1p |
| مصطلحات موضوعية: |
BIOLOGICAL transport, COMBINATION drug therapy, CHOLESTEROL, ELECTROPHORESIS, GLYCOPROTEINS, HIGH density lipoproteins, HYPERLIPIDEMIA, LIPOPROTEINS, PLACEBOS, QUINOLINE, STATISTICAL sampling, TREATMENT effectiveness, DESCRIPTIVE statistics, ROSUVASTATIN, CHEMICAL inhibitors |
| مستخلص: |
Background TA-8995 is a potent inhibitor of cholesteryl ester transfer protein (CETP) with beneficial effects on lipids and lipoproteins. The effect of TA-8995 on cholesterol efflux capacity (CEC), a measure of high-density lipoprotein (HDL) function, and HDL subparticle distribution is largely unknown. Objective To assess the effect of the CETP inhibitor TA-8995 on ABCA1- and non–ABCA1-driven CEC and on HDL particle distribution. Methods Total, non–ABCA1-, and ABCA1-specific CEC from J774 cells and HDL subclass distribution assessed by two-dimensional gel electrophoresis were measured at baseline and after 12-week treatment in 187 mild-dyslipidemic patients randomized to placebo, 1 mg, 5 mg, 10 mg TA-8995, or 10 mg TA-8995 combined with 10 mg rosuvastatin (NCT01970215). Results Compared with placebo, total, non–ABCA1-, and ABCA1-specific CEC were increased dose dependently by up to 38%, 72%, and 28%, respectively, in patients randomized to 10 mg of TA-8995. PreBeta-1 HDL, the primary acceptor for ABCA1-driven cholesterol efflux, was increased by 36%. This increase in preBeta-1 HDL correlated significantly with the total and the ABCA1-driven CEC increase, whereas the high-density lipoprotein cholesterol (HDL-C) increase did not. Conclusion TA-8995 dose dependently increased not only total and non–ABCA1-specific CEC but also ABCA1-specific CEC and preBeta-1 HDL particle levels. These findings suggest that TA-8995 not only increases HDL-C levels but also promotes functional properties of HDL particles. This CETP inhibitor–driven preBeta-1 HDL increase is an important predictor of both ABCA1 and total CEC increase, independent of HDL-C increase. Whether these changes in HDL particle composition and functionality have a beneficial effect on cardiovascular outcome requires formal testing in a cardiovascular outcome trial. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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