Effects of atorvastatin on high-density lipoprotein apolipoprotein A-I metabolism in dogs

被引:13
作者
Briand, F
Magot, T
Krempf, M
Nguyen, P
Ouguerram, K
机构
[1] CHU Nantes, Ctr Rech Nutr Humaine, INSERM, U539, F-44093 Nantes 01, France
[2] Ecole Natl Vet Nantes, USC INRA Nutr & Endocrinol, Nantes, France
关键词
apo A-I; atorvastatin; CETP; dog; kinetics; lipoprotein;
D O I
10.1111/j.1365-2362.2006.01622.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background The mechanisms involved in the decline of high-density lipoprotein (HDL) levels at a higher dose of atorvastatin have not yet been elucidated. We investigated the effects of atorvastatin on HDL-apolipoprotein (apo) A-I metabolism in dogs, a species lacking cholesteryl ester transfer protein activity. Materials and methods Seven ovariectomized normolipidaemic female Beagle dogs underwent a primed constant infusion of [5,5,5-H-2(3)] leucine to determine HDL-apo A-I kinetics before and after atorvastatin treatment (5 mg kg(-1) d(-1) for 6 weeks). Plasma lipoprotein profiles, activity of HDL-modifying enzymes involved in reverse cholesterol transport and hepatic scavenger receptor class B type I (SR-BI) expression were also studied. Results Atorvastatin treatment decreased HDL-cholesterol levels (3.56 +/- 0.24 vs. 2.64 +/- 0.15 mmol L-1, P < 0.05). HDL-triglycerides were not affected. HDL-phospholipids levels were decreased (4.28 +/- 0.13 vs. 3.29 +/- 0.13 mmol L-1, P < 0.05), as well as phospholipids transfer protein (PLTP) activity (0.83 +/- 0.05 vs. 0.60 +/- 0.05 pmol mu L-1 min(-1), P < 0.05). Activity of lecithin: cholesterol acyl transferase (LCAT), hepatic lipase (HL) and SR-BI expression did not change. HDL-apo A-I absolute production rate (APR) was higher after treatment (twofold, P < 0.05) as well as fractional catabolic rate (FCR) (threefold, P < 0.05). This resulted in lower HDL-apo A-I levels (2.36 +/- 0.03 vs. 1.55 +/- 0.04 g l(-1), P < 0.05). Plasma lipoprotein profiles showed a decrease in large HDL1 levels, with lower apo A-I and higher apo E levels in this subfraction. Conclusion Although a high dose of atorvastatin up-regulated HDL-apo A-I production, this drug also increased HDL-apo A-I FCR in dogs. This effect could be explained by a higher uptake of apo E-enriched HDL1 by hepatic lipoprotein receptors.
引用
收藏
页码:224 / 230
页数:7
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