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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F18%3A50014686" target="_blank" >RIV/62690094:18470/18:50014686 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1038/s41598-018-32376-4" target="_blank" >http://dx.doi.org/10.1038/s41598-018-32376-4</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-018-32376-4" target="_blank" >10.1038/s41598-018-32376-4</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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 &lt; 0.05), whereas simvastatin dose-dependently abolished structural changes induced by LPS (p &lt; 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 &lt; 0.05), decreased cleaved caspase-3 expression (32.1 +/- 5.8%, p &lt; 0.01), along with significant Bcl-xL expression in the simvastatin groups (p &lt; 0.01). Interestingly, in the simvastatin groups were determined significantly increased expression of survivin (p &lt; 0.01), but in negative correlation with cleaved caspase-3 and apoptotic indices (p &lt; 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-kappa B, which leads to reduced activation of caspase-3 and consequent apoptosis of cardiomyocytes in experimental sepsis.

Název v anglickém jazyce

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

Popis výsledku anglicky

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 &lt; 0.05), whereas simvastatin dose-dependently abolished structural changes induced by LPS (p &lt; 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 &lt; 0.05), decreased cleaved caspase-3 expression (32.1 +/- 5.8%, p &lt; 0.01), along with significant Bcl-xL expression in the simvastatin groups (p &lt; 0.01). Interestingly, in the simvastatin groups were determined significantly increased expression of survivin (p &lt; 0.01), but in negative correlation with cleaved caspase-3 and apoptotic indices (p &lt; 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-kappa B, which leads to reduced activation of caspase-3 and consequent apoptosis of cardiomyocytes in experimental sepsis.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30108 - Toxicology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Scientific reports

ISSN

2045-2322

e-ISSN

—

Svazek periodika

8

Číslo periodika v rámci svazku

October

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

10

Strana od-do

"Article Number: 14652"

Kód UT WoS článku

000446034000053

EID výsledku v databázi Scopus

2-s2.0-85054183714