Simvastatin Protects Cardiomyocytes Against Endotoxin-induced Apoptosis and Up-regulates Survivin/NF-κB/p65 Expression

• Published in: Scientific reports Vol. 8; no. 1; pp. 14652 - 10
• Main Authors: Nežić, Lana, Škrbić, Ranko, Amidžić, Ljiljana, Gajanin, Radoslav, Kuča, Kamil, Jaćević, Vesna
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.10.2018; Nature Publishing Group
• Subjects: 13/2; 64; 692/308; 692/4019; Apoptosis; Bcl-x protein; Cardiomyocytes; Caspase; Caspase-3; Endotoxins; Humanities and Social Sciences; Inflammation; Lethal dose; Lipopolysaccharides; multidisciplinary; Myofibrils; NF-κB protein; Rodents; Science; Science (multidisciplinary); Sepsis; Simvastatin; Survivin; Simvastatin Group; Transferase-mediated dUTP Nick End Labeling (TUNEL); Experimental Sepsis; Apoptotic Index (AI); Sepsis-induced Myocardial Dysfunction (SIMD)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-32376-4

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 effect. Wistar rats were pretreated with simvastatin (10–40 mg/kg po ) before a single non-lethal dose of LPS. In myocardial tissue, LPS induced structural disorganization of myofibrils with significant inflammatory infiltrate (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 20 mg/kg and 40 mg/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 significant Bcl-xL expression in the simvastatin groups ( p  < 0.01). Interestingly, in the simvastatin groups were determined significantly 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 effects against LPS induced apoptosis. The effect 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.