Atorvastatin reduces CD68, FABP4, and HBP expression in oxLDL-treated human macrophages.
With the aim of identifying new target genes that could contribute to limit foam cell formation, we analyzed changes in the pattern of gene expression in human THP-1 macrophages treated with atorvastatin and oxidized-LDL (oxLDL). To this end, we used a human cDNA array containing 588 cardiovascular-related cDNAs. Exposure to oxLDL resulted in differential expression of 26 genes, while coincubation with atorvastatin modified the expression of 29 genes, compared to treatment with oxLDL alone. Changes in the expression of candidate genes, potentially connected to the atherosclerotic process, were confirmed by quantitative RT-PCR and Western blot. We show that atorvastatin prevents the increase in the expression of scavenger receptor CD68 and that of fatty acid binding protein 4 caused by oxLDL. In addition, atorvastatin reduces the expression of HDL-binding protein, apolipoprotein E, and matrix metalloproteinase 9. These findings are relevant to understand the direct antiatherogenic effects of statins on macrophages.
Llaverias
Gemma
G
Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona, Spain.
Noé
Véronique
V
Peñuelas
Silvia
S
Vázquez-Carrera
Manuel
M
Sánchez
Rosa M
RM
Laguna
Juan C
JC
Ciudad
Carlos J
CJ
Alegret
Marta
M
D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis* / Q000235:genetics; D001057:Apolipoproteins E / Q000096:biosynthesis; D000069059:Atorvastatin; D001345:Autoradiography; D015153:Blotting, Western; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D030562:Databases, Protein; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D026563:LDL-Receptor Related Protein-Associated Protein / Q000096:biosynthesis* / Q000235:genetics; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000096:biosynthesis; D011758:Pyrroles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001057:Apolipoproteins E; D000069059:Atorvastatin; D002352:Carrier Proteins; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D006538:Heptanoic Acids; D026563:LDL-Receptor Related Protein-Associated Protein; D008077:Lipoproteins, LDL; D008666:Metalloendopeptidases; D011758:Pyrroles; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C493410:FABP4 protein, human; C107608:FABP7 protein, human; C099252:oxidized low density lipoprotein