Atorvastatin decreases lipoprotein lipase and endothelial lipase expression in human THP-1 macrophages
| Autor: | John S. Hill, Guosong Qiu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Endothelial lipase
medicine.medical_specialty Atorvastatin Receptors Cytoplasmic and Nuclear QD415-436 Biology Reductase Biochemistry Cell Line Endocrinology Polyisoprenyl Phosphates Internal medicine medicine Animals Humans simvastatin THP1 cell line Pyrroles cardiovascular diseases Liver X receptor Liver X Receptors Lipoprotein lipase Dose-Response Relationship Drug Activator (genetics) Macrophages NF-kappa B Rho protein nutritional and metabolic diseases Cell Biology Lipase Orphan Nuclear Receptors 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor DNA-Binding Proteins Lipoprotein Lipase Gene Expression Regulation Simvastatin Heptanoic Acids Hydroxymethylglutaryl CoA Reductases lipids (amino acids peptides and proteins) Hydroxymethylglutaryl-CoA Reductase Inhibitors Sesquiterpenes nuclear factor κB medicine.drug liver X receptor |
| Zdroj: | Journal of Lipid Research, Vol 48, Iss 10, Pp 2112-2122 (2007) |
| ISSN: | 0022-2275 |
| Popis: | Macrophage-derived lipases are associated with atherosclerosis in human and animal studies. Despite nu- merous non-lipid-lowering effects of statins, their effect on macrophage LPL and endothelial lipase (EL) expression has not been investigated. In the present study, atorvasta- tin and simvastatin dose-dependently decreased LPL and EL expression as well as Rho, liver X receptor a (LXRa), and nuclear factor kB (NF-kB) activation in THP-1 macro- phages. Atorvastatin-reduced LPL and EL expression was only partially recovered by mevalonate cotreatment, indicat- ing that mechanisms independent of reductase inhibition may be present. By contrast, Rho activation by lysophospha- tidyl acid further decreased LPL and EL expression in the presence or absence of atorvastatin. Another Rho activator, farnysyl pyrophosphate, decreased EL expression only in the absence of atorvastatin. LXRa activation by T0901317 and 22(R)-hydroxycholesterol not only rescued but also sig- nificantly increased LPL expression in the presence and absence of atorvastatin, respectively, whereas LXRa inhibi- tion by 22(S)-hydroxycholesterol decreased LPL expression. By contrast, EL expression was suppressed by LXRa activa- tion in the presence or absence of atorvastatin. NF-kB in- hibition by SN50 was associated with an ?30% reduction of EL expression. Furthermore, atorvastatin treatment signif- icantly attenuated the lipid accumulation in macrophages treated with oxidized LDL. We conclude that atorvastatin reduces LPL and EL expression by reducing the activation of LXRa and NF-kB, respectively.—Qiu, G. and J. S. Hill. Atorvastatin decreases lipoprotein lipase and endothelial lipase expression in human THP-1 macrophages. J. Lipid Res. 2007. 48: 2112-2122. |
| Databáze: | OpenAIRE |
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