Simvastatin attenuates cardiopulmonary bypass-induced myocardial inflammatory injury in rats by activating peroxisome proliferator-activated receptor γ

Statins have been shown to downregulate the systemic inflammatory response after cardiopulmonary bypass However the role of statins as anti inflammatory agents in heart tissue remains unknown The aim of this study was to test whether statin pretreatment attenuates local inflammatory cytokines production in heart and to explore whether the underlying mechanism involves peroxisome proliferator activated receptor (PPAR) gamma A rat model of cardiopulmonary bypass was established The animals were pretreated with simvastatin 5 mg/kg/day or 10 mg/kg/day for 7 days before operation The serum concentration and myocardial level of tumor necrosis factor (TNF)-alpha interleukin (IL) 6 monocyte chemoattractant protein (MCP) 1 was evaluated by enzyme linked immunosorbent assay The polymorphonuclear neutrophils accumulation in heart tissue was determined by myeloperoxidase activity assay The activity of nuclear factor (NF) kappa B and PPAR gamma in the heart was determined by electrophoretic mobility shift assay The myocardial PPAR gamma expression was also examined by immunohistochemistry The systemic and local TNF-alpha IL-6 and MCP 1 were all significantly elevated after cardiopulmonary bypass In contrast simvastatin pretreatment significantly decreases the serum and myocardial expression level of above cytokines myocardial myeloperoxidase activity and myocardial NF-kappa B activity However there was an evident increase in the activity and expression of PPAR gamma In conclusion simvastatin pretreatment not only attenuates acute systemic and local inflammatory response induced by cardiopulmonary bypass The anti-inflammatory effect of simvastatin in myocardium may be partly related to the activation of PPAR gamma and inhibition of NF kappa B (C) 2010 Elsevier B V All rights reserved