Simvastatin inhibits C-reactive protein-induced pro-inflammatory changes in endothelial cells by decreasing...

The effects of HMG-CoA reductase inhibitors on C-reactive protein (CRP)-induced pro-inflammatory changes in endothelial cells remain unclear. We tested the hypothesis that simvastatin inhibited CRP-induced pro-inflammatory changes in endothelial cells by decreasing mevalonate pathway products.

Human umbilical vein endothelial cells were incubated with CRP and measurement of CD32, nuclear factor kappaB (NF-kappaB) activation, vascular cell adhesion molecule-1 expression and monocyte adhesion assay were performed. The effects of simvastatin, siRNA against CD32 (siCD32) and mevalonate pathway products were also examined.

Pre-treatment with simvastatin significantly attenuated the CRP-induced CD32 expression and NF-kappaB activation in human umbilical vein endothelial cells. Simvastatin also decreased CRP-induced vascular cell adhesion molecule-1 expression and reduced monocyte adhesion on endothelial cells. The inhibitory effects of simvastatin were significantly reversed by adding mevalonate and geranylgeranyl pyrophosphate (GGPP), but not by adding farnesyl pyrophosphate. Pre-treatment with siCD32 also decreased CRP-induced CD32 expression and inhibitor of kappaB degradation. However, neither mevalonate nor GGPP reversed the effects of siCD32.

CRP-induced CD32 expression and NF-kappaB activation were attenuated by simvastatin. A decrease in mevalonate and subsequent GGPP contributes to the inhibitory effects of simvastatin. These findings may provide an explanation of using statins on patients with high serum CRP levels.