This study is aimed to investigate whether simvastatin induces cardiomyocytes survival signaling in
endotoxin (lipopolysaccharide, LSP)-induced myocardial injury, and if so, further to determine a role of
survivin in simvastatin-anti-apoptotic efect. Wistar rats were pretreated with simvastatin (10–40mg/kg
po) before a single non-lethal dose of LPS. In myocardial tissue, LPS induced structural disorganization
of myofbrils with signifcant infammatory infltrate (cardiac damage score, CDS=3.87±0.51,
p<0.05), whereas simvastatin dose-dependently abolished structural changes induced by LPS
(p<0.01). Simvastatin in 20mg/kg and 40mg/kg pretreatment, dose dependently, attenuated
myocardial apoptosis determined as apoptotic index (28.8±4.5% and 18.9±3.5, p<0.05), decreased
cleaved caspase-3 expression (32.1±5.8%, p<0.01), along with signifcant Bcl-xL expression in the
simvastatin groups (p<0.01). Interestingly, in the simvastatin groups were determined signifcantly
increased expression of survivin (p<0.01), but in negative correlation with cleaved caspase-3 and
apoptotic indices (p<0.01). Simvastatin has a cardioprotective efects against LPS induced apoptosis.
The efect may be mediated by up-regulation of survivin via activation of NF-κB, which leads to reduced
activation of caspase-3 and consequent apoptosis of cardiomyocytes in experimental sepsis.
