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Simvastatin Protects Cardiomyocytes Against Endotoxin-induced Apoptosis and Up-regulates Survivin/NF-κB/p65 Expression
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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168467/ https://www.ncbi.nlm.nih.gov/pubmed/30279549 http://dx.doi.org/10.1038/s41598-018-32376-4 |
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author | Nežić, Lana Škrbić, Ranko Amidžić, Ljiljana Gajanin, Radoslav Kuča, Kamil Jaćević, Vesna |
author_facet | Nežić, Lana Škrbić, Ranko Amidžić, Ljiljana Gajanin, Radoslav Kuča, Kamil Jaćević, Vesna |
author_sort | Nežić, Lana |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6168467 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61684672018-10-05 Simvastatin Protects Cardiomyocytes Against Endotoxin-induced Apoptosis and Up-regulates Survivin/NF-κB/p65 Expression Nežić, Lana Škrbić, Ranko Amidžić, Ljiljana Gajanin, Radoslav Kuča, Kamil Jaćević, Vesna Sci Rep Article 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. Nature Publishing Group UK 2018-10-02 /pmc/articles/PMC6168467/ /pubmed/30279549 http://dx.doi.org/10.1038/s41598-018-32376-4 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Nežić, Lana Škrbić, Ranko Amidžić, Ljiljana Gajanin, Radoslav Kuča, Kamil Jaćević, Vesna Simvastatin Protects Cardiomyocytes Against Endotoxin-induced Apoptosis and Up-regulates Survivin/NF-κB/p65 Expression |
title | Simvastatin Protects Cardiomyocytes Against Endotoxin-induced Apoptosis and Up-regulates Survivin/NF-κB/p65 Expression |
title_full | Simvastatin Protects Cardiomyocytes Against Endotoxin-induced Apoptosis and Up-regulates Survivin/NF-κB/p65 Expression |
title_fullStr | Simvastatin Protects Cardiomyocytes Against Endotoxin-induced Apoptosis and Up-regulates Survivin/NF-κB/p65 Expression |
title_full_unstemmed | Simvastatin Protects Cardiomyocytes Against Endotoxin-induced Apoptosis and Up-regulates Survivin/NF-κB/p65 Expression |
title_short | Simvastatin Protects Cardiomyocytes Against Endotoxin-induced Apoptosis and Up-regulates Survivin/NF-κB/p65 Expression |
title_sort | simvastatin protects cardiomyocytes against endotoxin-induced apoptosis and up-regulates survivin/nf-κb/p65 expression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168467/ https://www.ncbi.nlm.nih.gov/pubmed/30279549 http://dx.doi.org/10.1038/s41598-018-32376-4 |
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