Rosuvastatin suppresses the inflammatory responses through inhibition of c-Jun N-terminal kinase and Nuclear Factor-kappaB in endothelial cells.J Cardiovasc Pharmacol. 2007 Jun; 49(6):376-83.JC
Rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has pleiotropic effects that are anti-inflammatory and antiatherothrombotic. It is important to understand the cardioprotective effects of rosuvastatin in order to optimize its additional advantages in the treatment and prevention of cardiovascular diseases.
Human umbilical vein endothelial cells (HUVEC) were treated with tumor necrosis factor (TNF)-alpha (10 ng/mL) alone or with rosuvastatin (100 microM). The extent of inflammation was determined by U937 adhesion assay as well as analysis of the expression of intercellular adhesion molecule (ICAM)-1, monocyte chemoattractant protein (MCP)-1, interleukin (IL)-8, IL-6, cyclooxygenase (COX)-2, c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), p38, and signal transducer and activator of transcription (STAT)-3. The activation of nuclear factor kappa B (NF-kappaB) was determined by Western blot.
Rosuvastatin decreased the extent of U937 adhesion to TNF-alpha-stimulated HUVEC. Rosuvastatin inhibited the expressions of ICAM-1, MCP-1, IL-8, IL-6, and COX-2 mRNA and protein levels. The activation of JNK and NF-kappaB was also blocked by rosuvastatin. The inhibitors of JNK, NF-kappaB, and STAT-3 produced a statistically significant decrease of the TNF-alpha induced U937 adhesion and IL-6 protein release.
This study suggests that the anti-inflammatory activity of rosuvastatin is accompanied by the inhibition of JNK and NF-kappaB.