• This record comes from PubMed

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

. 2018 Oct 02 ; 8 (1) : 14652. [epub] 20181002

Language English Country England, Great Britain Media electronic

Document type Journal Article, Research Support, Non-U.S. Gov't

Links

PubMed 30279549
PubMed Central PMC6168467
DOI 10.1038/s41598-018-32376-4
PII: 10.1038/s41598-018-32376-4
Knihovny.cz E-resources

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.

See more in PubMed

Li Y, Ge S, Peng Y. Inflammation and cardiac dysfunction during sepsis, muscular dystrophy, and myocarditis. Burns Trauma. 2013;1:109–121. doi: 10.4103/2321-3868.123072. PubMed DOI PMC

Romero-Bermejo FJ, et al. Sepsis-induced cardiomyopathy. Curr. Cardiol. Rev. 2011;7:163–183. doi: 10.2174/157340311798220494. PubMed DOI PMC

Hobai IA, et al. Dysregulation of intracellular calcium transporters in animal models of sepsis induced cardiomyopathy. Shock. 2015;43:3–15. doi: 10.1097/SHK.0000000000000261. PubMed DOI PMC

Cimolai MC, et al. Mitochondrial Mechanisms in Septic Cardiomyopathy. Int. J. Mol. Sci. 2015;16:17763–17778. doi: 10.3390/ijms160817763. PubMed DOI PMC

Smeding L, et al. Structural changes of the heart during severe sepsis or septic shock. Shock. 2012;37:449–456. doi: 10.1097/SHK.0b013e31824c3238. PubMed DOI

Lancel S, et al. Ventricular myocyte caspases are directly responsable for endotoxin-induced cardiac dysfunction. Circulation. 2005;111:2596–2604. doi: 10.1161/CIRCULATIONAHA.104.490979. PubMed DOI

Buerke U, et al. Apoptosis contributes to septic cardiomyopathy and is improved by simvastatin therapy. Shock. 2008;29:497–503. doi: 10.1097/SHK.0b013e318142c434. PubMed DOI

Fauvel H, Marchetti P, Chopin C, Formstecher P, Neviere R. Differential effects of caspase inhibitors on endotoxin-induced myocardial dysfunction and heart apoptosis. Am. J. Physiol. Heart. Circ. Physiol. 2001;280:H1608–H1614. doi: 10.1152/ajpheart.2001.280.4.H1608. PubMed DOI

Nežić L, et al. Effect of simvastatin on proinflammatory cytokines production during lipopolysaccharide-induced inflammation in rats. Gen. Physiol. Biophys. 2009;28:119–126. PubMed

Nežić L, et al. Simvastatin and indomethacin have similar anti-inflammatory activity in a rat model of acute local inflammation. Basic Clin. Pharmacol. Toxicol. 2009;104:185–191. doi: 10.1111/j.1742-7843.2008.00302.x. PubMed DOI

Slotta JE, et al. Inhibition of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase reduces leukocyte recruitment and hepatocyte apoptosis in endotoxin-induced liver injury. J. Investig. Med. 2009;57:645–649. doi: 10.2310/JIM.0b013e3181a23cb0. PubMed DOI

Wang Y, et al. An experimental study of the protective effect of simvastatin on sepsis-induced myocardial depression in rats. Biomed. Pharmac. Ther. 2017;94:705–711. doi: 10.1016/j.biopha.2017.07.105. PubMed DOI

Tsang TJ, et al. Subcellular Localization of Survivin Determines Its Function in Cardiomyocytes. Theranostics. 2017;7:4577–4590. doi: 10.7150/thno.20005. PubMed DOI PMC

Dutta J, et al. Current insights into the regulation of programmed cell death by NF-kappaB. Oncogene. 2006;25:6800–6816. doi: 10.1038/sj.onc.1209938. PubMed DOI

Bo L, et al. Research on the function and mechanism of survivin in heart failure mice model. Eur. Rev. Med. Pharmacol. Sci. 2017;21:3699–3704. PubMed

Si R, et al. Survivin: a novel player in insulin cardioprotection against myocardial ischemia/reperfusion injury. J. Mol. Cell. Cardiol. 2011;50:16–24. doi: 10.1016/j.yjmcc.2010.08.017. PubMed DOI

Lee BS, et al. Insulin Protects Cardiac Myocytes from Doxorubicin Toxicity by Sp1-Mediated Transactivation of Survivin. PLoS ONE. 2015;10(8):e0135438. doi: 10.1371/journal.pone.0135438. PubMed DOI PMC

Chen CH, et al. Fluvastatin ameliorates endotoxin induced multiple organ failure in conscious rats. Resuscitation. 2007;74:166–174. doi: 10.1016/j.resuscitation.2006.12.002. PubMed DOI

La Mura V. Effects of simvastatin administration on rodents with lipopolysaccharide-induced liver microvascular dysfunction. Hepatology. 2013;57:1172–1181. doi: 10.1002/hep.26127. PubMed DOI

Liu X, et al. Effects of HMG-CoA reductase inhibitor on experimental autoimmune myocarditis. Cardiovasc. Drugs Ther. 2012;26:121–130. doi: 10.1007/s10557-012-6372-6. PubMed DOI

Chopra M, Sharma AC. Contractile response of norepinephrine is modulated by caspase-3 in adult rat ventricular myocytes isolated from septic rat heart. Pharmacol. Res. 2009;60:303–313. doi: 10.1016/j.phrs.2009.04.009. PubMed DOI PMC

Fu H, Wang QS, Luo Q. Simvastatin inhibits apoptosis of endothelial cells induced by sepsis through upregulating the expression of Bcl-2 and downregulating Bax. World J. Emerg. Med. 2014;5:291–297. doi: 10.5847/wjem.j.issn.1920-8642.2014.04.009. PubMed DOI PMC

Levkau B. Survivin signaling in the heart. J. Mol. Cell. Cardiol. 2011;50:6–8. doi: 10.1016/j.yjmcc.2010.10.013. PubMed DOI

Wilson RL, et al. Thioredoxin-1 attenuates sepsis-induced cardiomyopathy after cecal ligation and puncture in mice. J. Surg. Res. 2017;220:68–78. doi: 10.1016/j.jss.2017.06.062. PubMed DOI PMC

Wang K, et al. Survivin signaling is regulated through nuclear factor-kappa B pathway during glycochenodeoxycholate-induced hepatocyte apoptosis. Biochim. Biophys. Acta. 2010;12:1368–1375. doi: 10.1016/j.bbamcr.2010.08.008. PubMed DOI

Gyrd-Hansen M, Meier P. IAPs: from caspase inhibitors to modulators of NF-kappaB, inflammation and cancer. Nat. Rev. Cancer. 2010;10:561–574. doi: 10.1038/nrc2889. PubMed DOI

Wang Y, et al. Experimental Study of the Protective Effect of Simvastatin on Lung Injury in Rats with Sepsis. Inflammation. 2018;41:104–113. doi: 10.1007/s10753-017-0668-4. PubMed DOI

Shinozaki S, et al. Farnesyltransferase inhibitor improved survival following endotoxin challenge in mice. Biochem. Biophys. Res. Commun. 2010;391:1459–1464. doi: 10.1016/j.bbrc.2009.12.094. PubMed DOI PMC

Seemann S, Zohles F, Lupp A. Comprehensive comparison of three different animal models for systemic inflammation. J. Biomed. Sci. 2017;24:10–17. doi: 10.1186/s12929-017-0370-8. PubMed DOI PMC

Jaćević V, et al. Effects of fullerenol nanoparticles and amifostine on radiation-induced tissue damages: Histopathological analysis. J. Appl. Biomed. 2016;14:285–297. doi: 10.1016/j.jab.2016.05.004. DOI

Wu X, et al. N-acetylcysteine reduces oxidative stress, nuclear factor-κB activity and cardiomyocyte apoptosis in heart failure. Mol. Med. Rep. 2014;10:615–624. doi: 10.3892/mmr.2014.2292. PubMed DOI PMC

Zhang S, et al. Role of the JAK/STAT signaling pathway in the pathogenesis of acute myocardial infarction in rats and its effect on NF-κB expression. Mol. Med. Rep. 2013;7:93–98. doi: 10.3892/mmr.2012.1159. PubMed DOI

Newest 20 citations...

See more in
Medvik | PubMed

Overexpression of MRP1/ABCC1, Survivin and BCRP/ABCC2 Predicts the Resistance of Diffuse Large B-Cell Lymphoma to R-CHOP Treatment

. 2023 Aug 15 ; 15 (16) : . [epub] 20230815

Amelioration of Endotoxin-Induced Acute Lung Injury and Alveolar Epithelial Cells Apoptosis by Simvastatin Is Associated with Up-Regulation of Survivin/NF-kB/p65 Pathway

. 2022 Feb 26 ; 23 (5) : . [epub] 20220226

Antidotal Potency of the Novel, Structurally Different Adsorbents in Rats Acutely Intoxicated with the T-2 Toxin

. 2020 Oct 05 ; 12 (10) : . [epub] 20201005

Protective Effects of Simvastatin on Endotoxin-Induced Acute Kidney Injury through Activation of Tubular Epithelial Cells' Survival and Hindering Cytochrome C-Mediated Apoptosis

. 2020 Sep 30 ; 21 (19) : . [epub] 20200930

Acute Toxic Injuries of Rat's Visceral Tissues Induced by Different Oximes

. 2019 Nov 11 ; 9 (1) : 16425. [epub] 20191111

Simvastatin Inhibits Endotoxin-Induced Apoptosis in Liver and Spleen Through Up-Regulation of Survivin/NF-κB/p65 Expression

. 2019 ; 10 () : 54. [epub] 20190215

Toxic Injury to Muscle Tissue of Rats Following Acute Oximes Exposure

. 2019 Feb 06 ; 9 (1) : 1457. [epub] 20190206

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...