Effects of simvastation on homocysteine-induced endothelial dysfunction and inflammatory response and its molecular mechanisms

AIM: To investigate the effects of simvastation on homocysteine-induced endothelial dysfunction and inflammatory response and the underlying mechanisms of such effects. METHODS: MTT assay was used to detect cell viability, and DCFH-DA assay was used to examine the levels of reactive oxygen species (ROS). Furthermore, Western blotting was performed to detect protein expression and electrophoretic mobility shift assay (EMSA) was used to detect NF-κB DNA binding activity. RESULTS: Homocysteine (0.1-1 mmol/L) decreased the human umbilical vein endothelial cell (HUVEC) viability and increased the levels of ROS. Western blotting and ELISA showed that homocysteine significantly increased the expression of TNF-α, IL-6, MCP-1 and ICAM-1. However, pretreatment with simvastation (1-20 μmol/L) reversed the decreased cell viability and markedly suppressed an increase in the ROS level and the expression of TNF-α, IL-6, MCP-1 and ICAM-1 induced by homocysteine. Homocysteine induced p38 phosphorylation and such phosphorylation was also inhibited by simvastation and antioxidant NAC. EMSA and Western blotting showed that homocysteine induced NF-κB activation due to the increased phosphorylation of the inhibitory protein (IκBα) as well as the degradation of IκBα, while simvastation pretreatment almost completely blocked the NF-κB activation as well as the phosphorylation and degradation of IκBα. CONCLUSION: Simvastation inhibits homocysteine-induced endothelial dysfunction and inflammatory response through interfering with ROS-p38-NF-κB pathway.