Sirolimus upregulates aP2 expression in human monocytes and macrophages.
Rapamycin (Sirolimus) is a potent immunosuppressive drug that reduces renal transplant rejection. Hyperlipidemia is a significant side effect of rapamycin treatment, and frequently leads to cardiovascular disease. Adipocyte fatty acid binding protein (aP2) is a member of the cytoplasmic fatty acid binding protein (FABP) family. aP2 has been shown to affect insulin sensitivity, lipid metabolism, lipolysis, and has recently been shown to play an important role in atherosclerosis. We found that aP2 messenger RNA (mRNA) was increased in human THP-1 cells after rapamycin treatment. Exposure of human differentiated THP-1 cells to rapamycin led to a time- and dose-dependent induction of aP2 mRNA expression. While aP2 expression was undetectable in undifferentiated THP-1 cells, aP2 was induced in these cells by rapamycin. These data suggest that rapamycin-induced aP2 may play a role in increased triglyceride accumulation.
Liu
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Department of Cardiovascular and Metabolic Diseases Research, Wyeth Research, Collegeville, Pennsylvania 19246, USA. nambip@wyeth.com
Nambi
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D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D017931:DNA Primers; D050556:Fatty Acid-Binding Proteins; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020123:Sirolimus / Q000494:pharmacology*
D002352:Carrier Proteins; D017931:DNA Primers; D050556:Fatty Acid-Binding Proteins; D020123:Sirolimus