Functionality of postprandial larger HDL2 particles is enhanced following CETP inhibition therapy

Autor: Elise F. Villard, Natalie Fournier, Petra El Khoury, Emilie Duchene, Zélie Julia, Maryse Guerin, Wilfried Le Goff, M. John Chapman, Natacha Bellanger
Rok vydání: 2012
Předmět:
CD36 Antigens
Male
Time Factors
Atorvastatin
Mice
chemistry.chemical_compound
High-density lipoprotein
Cricetinae
ATP Binding Cassette Transporter
Subfamily G
Member 1
Hypolipidemic Agents
biology
Reverse cholesterol transport
Middle Aged
Postprandial Period
Lipoproteins
HDL2
Treatment Outcome
Postprandial
Liver
ABCG1
Quinolines
Drug Therapy
Combination
lipids (amino acids
peptides
and proteins)
Cholesterol Esters
Efflux
Cardiology and Cardiovascular Medicine
Apolipoprotein A-II
medicine.drug
Adult
Paris
medicine.medical_specialty
Hyperlipidemias
CHO Cells
Transfection
Cricetulus
Internal medicine
medicine
Animals
Humans
Pyrroles
Particle Size
Apolipoprotein A-I
Cholesterol
Macrophages
Cholesterol
HDL
Torcetrapib
Cholesterol Ester Transfer Proteins
Endocrinology
chemistry
Heptanoic Acids
biology.protein
ATP-Binding Cassette Transporters
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Zdroj: Atherosclerosis. 221:160-168
ISSN: 0021-9150
Popis: Objective To evaluate the impact of CETP inhibition on the capacity of individual postprandial HDL subspecies to promote key steps of the reverse cholesterol transport pathway. Methods The capacity of HDL particles to mediate cellular free cholesterol efflux and selective hepatic uptake of cholesteryl esters was evaluated throughout postprandial phase (0–8h) following consumption of a standardised mixed meal before and after treatment for 6 weeks with atorvastatin alone (10mg/d) and subsequently with combination torcetrapib/atorvastatin (60/10mg/d) in 16 patients displaying low HDL-C levels ( Results The larger HDL2b and HDL2a subfraction displayed a superior capacity to mediate cellular free cholesterol efflux via both SR-BI and ABCG1-dependent pathways than smaller HDL3 subspecies. CETP inhibition specifically enhanced the capacity of HDL2b subfraction for both SR-BI and ABCG1 dependent efflux. However, only the SR-BI-dependent efflux to HDL2b subspecies can be further enhanced during postprandial lipemia following CETP inhibition. Concomitantly, postprandial lipemia was associated with a reduced capacity of total HDL particles to deliver cholesteryl esters to hepatic cells in a drug independent manner. Conclusion CETP inhibition specifically improves postprandial SR-BI and ABCG1-dependent efflux to larger HDL2b subspecies. In addition, CETP inhibition improves HDL-CE delivery to hepatic cells and maintains an efficient direct return of cholesteryl esters to the liver during postprandial lipemia.
Databáze: OpenAIRE
Externí odkaz: