Tags

Type your tag names separated by a space and hit enter

Effects of atorvastatin on high-density lipoprotein apolipoprotein A-I metabolism in dogs.
Eur J Clin Invest. 2006 Apr; 36(4):224-30.EJ

Abstract

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-(2)H(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 microL(-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 HDL(1) levels, with lower apo A-I and higher apo E levels in this subfraction.

CONCLUSIONS

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 HDL(1) by hepatic lipoprotein receptors.

Authors+Show Affiliations

Centre de Recherche en Nutrition Humaine, INSERM U539, CHU Nantes, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16620283

Citation

Briand, F, et al. "Effects of Atorvastatin On High-density Lipoprotein Apolipoprotein A-I Metabolism in Dogs." European Journal of Clinical Investigation, vol. 36, no. 4, 2006, pp. 224-30.
Briand F, Magot T, Krempf M, et al. Effects of atorvastatin on high-density lipoprotein apolipoprotein A-I metabolism in dogs. Eur J Clin Invest. 2006;36(4):224-30.
Briand, F., Magot, T., Krempf, M., Nguyen, P., & Ouguerram, K. (2006). Effects of atorvastatin on high-density lipoprotein apolipoprotein A-I metabolism in dogs. European Journal of Clinical Investigation, 36(4), 224-30.
Briand F, et al. Effects of Atorvastatin On High-density Lipoprotein Apolipoprotein A-I Metabolism in Dogs. Eur J Clin Invest. 2006;36(4):224-30. PubMed PMID: 16620283.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of atorvastatin on high-density lipoprotein apolipoprotein A-I metabolism in dogs. AU - Briand,F, AU - Magot,T, AU - Krempf,M, AU - Nguyen,P, AU - Ouguerram,K, PY - 2006/4/20/pubmed PY - 2006/9/14/medline PY - 2006/4/20/entrez SP - 224 EP - 30 JF - European journal of clinical investigation JO - Eur J Clin Invest VL - 36 IS - 4 N2 - 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-(2)H(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 microL(-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 HDL(1) levels, with lower apo A-I and higher apo E levels in this subfraction. CONCLUSIONS: 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 HDL(1) by hepatic lipoprotein receptors. SN - 0014-2972 UR - https://www.unboundmedicine.com/medline/citation/16620283/Effects_of_atorvastatin_on_high_density_lipoprotein_apolipoprotein_A_I_metabolism_in_dogs_ L2 - https://doi.org/10.1111/j.1365-2362.2006.01622.x DB - PRIME DP - Unbound Medicine ER -