Statins synergize dexamethasone-induced adipocyte fatty acid binding protein expression in macrophages

Atherosclerosis, 06/04/2012

This study defines an important mechanism involved in the regulation of macrophage FABP4 expression by a glucocorticoid and statins.

Methods

  • Authors determined the effect of co–treatment of statins and dexamethasone on macrophage FABP4 expression.
  • Unexpectedly, statins did not block the induction of macrophage FABP4 expression by dexamethasone.
  • In contrast, statins synergized dexamethasone–induced FABP4 expression.
  • In vivo, pitavastatin synergized dexamethasone–induced FABP4 expression in both peritoneal macrophages and adipose tissues.
  • Cholesterol and mevalonate, but not farnesylation and geranylgeranylation, inhibited the synergistic induction.

Results

  • Promoter assay disclosed a putative negative glucocorticoid regulatory element (nGRE) in FABP4 gene.
  • Pitavastatin had little effect on expression of glucocorticoid receptor (GR).
  • However, pitavastatin enhanced dexamethasone–mediated GR nuclear translocation but inhibited the binding of GR with nGRE.

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