摘要
Objectives: 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. Methods: Human umbilical vein endothelial cells were incubated with CRP and measurement of CD32, nuclear factor κB (NF-κB) 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. Results: Pre-treatment with simvastatin significantly attenuated the CRP-induced CD32 expression and NF-κB 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 κB degradation. However, neither mevalonate nor GGPP reversed the effects of siCD32. Conclusions: CRP-induced CD32 expression and NF-κB 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.
原文 | 英語 |
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頁(從 - 到) | 182-190 |
頁數 | 9 |
期刊 | Cardiology |
卷 | 110 |
發行號 | 3 |
DOIs | |
出版狀態 | 已發佈 - 6月 2008 |
ASJC Scopus subject areas
- 心臟病學與心血管醫學