Simvastatin inhibits C-reactive protein-induced pro-inflammatory changes in endothelial cells by decreasing mevalonate pathway products

Yao J. Liang, Kou G. Shyu, Bao W. Wang, Ling Ping Lai

研究成果: 雜誌貢獻文章同行評審

22 引文 斯高帕斯(Scopus)

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
頁(從 - 到)182-190
頁數9
期刊Cardiology
110
發行號3
DOIs
出版狀態已發佈 - 六月 2008

ASJC Scopus subject areas

  • 心臟病學與心血管醫學

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