Atorvastatin decreases stearoyl-CoA desaturase gene expression in THP-1 macrophages incubated with oxidized LDL.
Statins, inhibitors of HMG-CoA reductase, reduce plasma low-density lipoprotein (LDL) cholesterol levels decreasing the incidence of coronary events. However, the observed benefit of statins appears to extend beyond their lipid-lowering effects. Previous studies by our group have demonstrated that atorvastatin in oxidized LDL incubated macrophages modifies the gene expression profile of certain enzymes involved in fatty acid metabolism, mainly stearoyl-CoA desaturase (SCD). SCD is a rate-limiting enzyme in the biosynthesis of monounsaturated fatty acids and its expression is mediated by sterol regulatory element-binding protein-1 (SREBP-1). The aim of this study was to determine whether atorvastatin might affect the fatty acid composition in macrophages and if their SCD gene expression profile could explain this effect. Therefore, THP-1 macrophages were treated with atorvastatin and native or oxidized LDL, their fatty acid composition was determined by gas-chromatography, and the SCD and SREBP-1 gene expression profile was analysed using quantitative RT-PCR. We found that atorvastatin reduces the percentage of palmitoleic and oleic acids in THP-1 cells incubated with oxLDL, which could be explained by the inhibition of SCD and SREBP-1 gene expression. The observed results were reversed when mevalonate was added to THP-1 macrophages. This would suggest that inhibition of SCD in THP-1 macrophages incubated with oxLDL and the change in fatty acid composition is an important effect of atorvastatin.
Martín-Fuentes
Paula
P
Laboratorio de Investigación Molecular, Instituto Aragonés de Ciencias de la Salud (I+CS), Hospital Universitario Miguel Servet, Edificio de Consultas Externas, planta 4 feminine, c/ Cardenal Gomá, s/n, 50009 Zaragoza, Spain. pmartin.iacs@aragon.es
García-Otín
Angel Luis
AL
Calvo
Luisa
L
Gómez-Coronado
Diego
D
Civeira
Fernando
F
Cenarro
Ana
A
D000069059:Atorvastatin; D002460:Cell Line; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology*; D013230:Stearoyl-CoA Desaturase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000096:biosynthesis
D005231:Fatty Acids, Unsaturated; D006538:Heptanoic Acids; D008077:Lipoproteins, LDL; D011758:Pyrroles; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; C099252:oxidized low density lipoprotein; D000069059:Atorvastatin; D013230:Stearoyl-CoA Desaturase