Statin-Induced Decrease in ATP-Binding Cassette Transporter A1 Expression via microRNA33 Induction may Counteract Cholesterol Efflux to High-Density Lipoprotein
Autor: | Eric J. Niesor, David Kallend, Gabriela Bucklar-Suchankova, Markus Abt, Andrea Stauffer, Gregory G. Schwartz, Alexandre Durrwell, Renée Benghozi, Anne Perez |
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Rok vydání: | 2015 |
Předmět: |
Simvastatin
Dalcetrapib Pharmacology Cholesterol 7 alpha-hydroxylase Cell Line Mice chemistry.chemical_compound polycyclic compounds Animals Humans Medicine Pharmacology (medical) Rosuvastatin RNA Messenger cardiovascular diseases Pitavastatin ATP Binding Cassette Transporter Subfamily G Member 1 biology business.industry Cholesterol Reverse cholesterol transport nutritional and metabolic diseases General Medicine MicroRNAs Receptors LDL chemistry Biochemistry ABCA1 HMG-CoA reductase biology.protein ATP-Binding Cassette Transporters lipids (amino acids peptides and proteins) Hydroxymethylglutaryl-CoA Reductase Inhibitors Lipoproteins HDL Cardiology and Cardiovascular Medicine business ATP Binding Cassette Transporter 1 medicine.drug |
Zdroj: | Cardiovascular Drugs and Therapy. 29:7-14 |
ISSN: | 1573-7241 0920-3206 |
Popis: | Cholesterol efflux from macrophages to HDL, measured in vitro, is augmented by treatment with agents which raise HDL cholesterol. In vitro, cholesterol depletion by statins is known to trigger a positive feedback on the cholesterol synthetic pathway via sterol regulatory element-binding protein (SREBP) transcription and changes in expression of SREBP regulated genes including microRNA33 (miR33) which is co-transcribed with SREBP and down-regulates ABCA1 and ABCG1 expression.We investigated whether miR33 up-regulation, associated with SREBP increased transcription by statins, reduces macrophage ATP-binding cassette (ABC) transporter expression, thereby decreasing HDL-mediated cholesterol efflux at the tissue level.In human macrophage THP-1 cells cholesterol-loaded with acetylated LDL, incubation with 1 μM atorvastatin increased miR33 by 33 % (P 0.05), and decreased ABCA1 messenger RNA (mRNA) and ABCG1 mRNA by 47 % (P 0.05) and 27 % (NS), respectively. In J774A.1 mouse macrophage, labelled with 3H-cholesterol, ABCA1 mRNA and ABCA1-mediated cholesterol efflux were decreased by 1 μM statin: simvastatinpitavastatinatorvastatinrosuvastatinpravastatin. HDL incubated with rhCETP and dalcetrapib increased ABCA1-mediated cholesterol efflux. However, incremental simvastatin concentrations decreased cholesterol efflux to HDL treated with rhCETP and dalcetrapib. When HDL was incubated with rhCETP, addition of dalcetrapib augmented ABCA1-mediated cholesterol efflux from J774A.1 macrophages. However, simvastatin ≥1 μM virtually eliminated any HDL-ABCA1-mediated cholesterol efflux and any augmentation of that process by dalcetrapib.In vitro, statins increase miR33 expression, and decrease ABCA1 expression and cholesterol efflux from peripheral tissues; this may counteract the potential benefit of agents that raise HDL and apolipoprotein A-I in statin-treated patients. |
Databáze: | OpenAIRE |
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