Cholesteryl Ester Transfer Protein Inhibition With Anacetrapib Decreases Fractional Clearance Rates of High-Density Lipoprotein Apolipoprotein A-I and Plasma Cholesteryl Ester Transfer Protein
| Autor: | Patricia Jumes, Rajasekhar Ramakrishnan, Stephen Holleran, John S. Millar, Gissette Reyes-Soffer, Amanda Baer, Yang Liu, Henry N. Ginsberg, Tiffany Thomas, David E. Gutstein, John A. Wagner, Amy O. Johnson-Levonas, Richard L. Dunbar, Emil M. deGoma, Daniel J. Rader, Michael E. Lassman, Wahida Karmally, Colleen Ngai, Ellie Coromilas, Hashmi Rafeek, Daniel S. Donovan, Bela F. Asztalos |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Time Factors Apolipoprotein B Atorvastatin 030204 cardiovascular system & hematology Fractional clearance 03 medical and health sciences Plasma Cholesteryl Ester Transfer Protein chemistry.chemical_compound 0302 clinical medicine High-density lipoprotein Double-Blind Method Anacetrapib Internal medicine Cholesterylester transfer protein medicine Humans Oxazolidinones Aged Dyslipidemias Apolipoprotein A-I biology Chemistry Anticholesteremic Agents nutritional and metabolic diseases Metabolism Middle Aged Cholesterol Ester Transfer Proteins Treatment Outcome 030104 developmental biology Endocrinology biology.protein Female lipids (amino acids peptides and proteins) Lipoproteins HDL Cardiology and Cardiovascular Medicine Apolipoprotein A-II Biomarkers medicine.drug |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 36:994-1002 |
| ISSN: | 1524-4636 1079-5642 |
| Popis: | Objective— Anacetrapib (ANA), an inhibitor of cholesteryl ester transfer protein (CETP) activity, increases plasma concentrations of high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-I (apoA)-I, apoA-II, and CETP. The mechanisms responsible for these treatment-related increases in apolipoproteins and plasma CETP are unknown. We performed a randomized, placebo (PBO)-controlled, double-blind, fixed-sequence study to examine the effects of ANA on the metabolism of HDL apoA-I and apoA-II and plasma CETP. Approach and Results— Twenty-nine participants received atorvastatin (ATV) 20 mg/d plus PBO for 4 weeks, followed by ATV plus ANA 100 mg/d for 8 weeks (ATV-ANA). Ten participants received double PBO for 4 weeks followed by PBO plus ANA for 8 weeks (PBO-ANA). At the end of each treatment, we examined the kinetics of HDL apoA-I, HDL apoA-II, and plasma CETP after D3-leucine administration as well as 2D gel analysis of HDL subspecies. In the combined ATV-ANA and PBO-ANA groups, ANA treatment increased plasma HDL-C (63.0%; P P P =0.002) without changes in production rate. Although the apoA-II levels increased by 12.6% ( P P P Conclusions— ANA treatment increases HDL apoA-I and CETP levels by decreasing the fractional clearance rate of each protein. |
| Databáze: | OpenAIRE |
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