Acute doxorubicin-induced cardiotoxicity is associated with matrix metalloproteinase-2 alterations in rats
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://www.karger.com/Article/FullText/374001 http://hdl.handle.net/11449/128314 |
Resumo: | Background: Doxorubicin can cause cardiotoxicity. Matrix metalloproteinases (MMP) are responsible for degrading extracellular matrix components which play a role in ventricular dilation. Increased MMP activity occurs after chronic doxorubicin treatment. In this study we evaluated in vivo and in vitro cardiac function in rats with acute doxorubicin treatment, and examined myocardial MMP and inflammatory activation, and gene expression of proteins involved in myocyte calcium transients. Methods: Wistar rats were injected with doxorubicin (Doxo, 20 mg/kg) or saline (Control). Echocardiogram was performed 48 h after treatment. Myocardial function was assessed in vitro in Langendorff preparation. Results: In left ventricle, doxorubicin impaired fractional shortening (Control 0.59 +/- 0.07; Doxo 0.51 +/- 0.05; p < 0.001), and increased isovolumetric relaxation time (Control 20.3 +/- 4.3; Doxo 24.7 +/- 4.2 ms; p = 0.007) and myocardial passive stiffness. MMP-2 activity, evaluated by zymography, was increased in Doxo (Control 141338 +/- 8924; Doxo 188874 +/- 7652 arbitrary units; p < 0.001). There were no changes in TNF-alpha, INF-gamma, IL-10, and ICAM-1 myocardial levels. Expression of phospholamban, Serca-2a, and ryanodine receptor did not differ between groups. Conclusion: Acute doxorubicin administration induces in vivo left ventricular dysfunction and in vitro increased myocardial passive stiffness in rats. Cardiac dysfunction is related to myocardial MMP-2 activation. Increased inflammatory stimulation or changed expression of the proteins involved in intracellular calcium transients is not involved in acute cardiac dysfunction. |
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Acute doxorubicin-induced cardiotoxicity is associated with matrix metalloproteinase-2 alterations in ratsIsolated heart studyCytokinesPhospholambanRyanodine receptorSerca-2aMatrix metalloproteinaseDoxorubicinAcute cardiotoxicityBackground: Doxorubicin can cause cardiotoxicity. Matrix metalloproteinases (MMP) are responsible for degrading extracellular matrix components which play a role in ventricular dilation. Increased MMP activity occurs after chronic doxorubicin treatment. In this study we evaluated in vivo and in vitro cardiac function in rats with acute doxorubicin treatment, and examined myocardial MMP and inflammatory activation, and gene expression of proteins involved in myocyte calcium transients. Methods: Wistar rats were injected with doxorubicin (Doxo, 20 mg/kg) or saline (Control). Echocardiogram was performed 48 h after treatment. Myocardial function was assessed in vitro in Langendorff preparation. Results: In left ventricle, doxorubicin impaired fractional shortening (Control 0.59 +/- 0.07; Doxo 0.51 +/- 0.05; p < 0.001), and increased isovolumetric relaxation time (Control 20.3 +/- 4.3; Doxo 24.7 +/- 4.2 ms; p = 0.007) and myocardial passive stiffness. MMP-2 activity, evaluated by zymography, was increased in Doxo (Control 141338 +/- 8924; Doxo 188874 +/- 7652 arbitrary units; p < 0.001). There were no changes in TNF-alpha, INF-gamma, IL-10, and ICAM-1 myocardial levels. Expression of phospholamban, Serca-2a, and ryanodine receptor did not differ between groups. Conclusion: Acute doxorubicin administration induces in vivo left ventricular dysfunction and in vitro increased myocardial passive stiffness in rats. Cardiac dysfunction is related to myocardial MMP-2 activation. Increased inflammatory stimulation or changed expression of the proteins involved in intracellular calcium transients is not involved in acute cardiac dysfunction.Universidade Estadual Paulista, Departamento de Clínica Médica, Faculdade de Medicina de BotucatuUniversidade Estadual Paulista, Departamento de Morfologia, Instituto de Biociências de BotucatuUniversidade Estadual Paulista, Departamento de Microbiologia e Imunologia, Instituto de Biociências de BotucatuKargerUniversidade Estadual Paulista (Unesp)Polegato, Bertha Furlan [UNESP]Minicucci, Marcos Ferreira [UNESP]Azevedo, Paula Schmidt [UNESP]Carvalho, Robson Francisco [UNESP]Chiuso-Minicucci, Fernanda [UNESP]Pereira, Elenize Jamas [UNESP]Paiva, Sergio Alberto Rupp [UNESP]Zornoff, Leonardo Antonio Mamede [UNESP]Okoshi, Marina Politi [UNESP]Matsubara, Beatriz Bojikian [UNESP]Matsubara, Luiz Shiguero [UNESP]2015-10-21T13:08:55Z2015-10-21T13:08:55Z2015-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1924-1933application/pdfhttp://www.karger.com/Article/FullText/374001Cellular Physiology And Biochemistry. Basel: Karger, v. 35, n. 5, p. 1924-1933, 2015.1015-8987http://hdl.handle.net/11449/12831410.1159/000374001WOS:000353713900022WOS000353713900022.pdf54065187991284856990977122340795446313867199843263098351379987665016839015394547121314080140264774387040344716730000-0002-4901-77140000-0002-9831-88200000-0002-5843-6232Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengCellular Physiology And Biochemistry5.5001,561info:eu-repo/semantics/openAccess2024-08-14T17:22:14Zoai:repositorio.unesp.br:11449/128314Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-14T17:22:14Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Acute doxorubicin-induced cardiotoxicity is associated with matrix metalloproteinase-2 alterations in rats |
title |
Acute doxorubicin-induced cardiotoxicity is associated with matrix metalloproteinase-2 alterations in rats |
spellingShingle |
Acute doxorubicin-induced cardiotoxicity is associated with matrix metalloproteinase-2 alterations in rats Polegato, Bertha Furlan [UNESP] Isolated heart study Cytokines Phospholamban Ryanodine receptor Serca-2a Matrix metalloproteinase Doxorubicin Acute cardiotoxicity |
title_short |
Acute doxorubicin-induced cardiotoxicity is associated with matrix metalloproteinase-2 alterations in rats |
title_full |
Acute doxorubicin-induced cardiotoxicity is associated with matrix metalloproteinase-2 alterations in rats |
title_fullStr |
Acute doxorubicin-induced cardiotoxicity is associated with matrix metalloproteinase-2 alterations in rats |
title_full_unstemmed |
Acute doxorubicin-induced cardiotoxicity is associated with matrix metalloproteinase-2 alterations in rats |
title_sort |
Acute doxorubicin-induced cardiotoxicity is associated with matrix metalloproteinase-2 alterations in rats |
author |
Polegato, Bertha Furlan [UNESP] |
author_facet |
Polegato, Bertha Furlan [UNESP] Minicucci, Marcos Ferreira [UNESP] Azevedo, Paula Schmidt [UNESP] Carvalho, Robson Francisco [UNESP] Chiuso-Minicucci, Fernanda [UNESP] Pereira, Elenize Jamas [UNESP] Paiva, Sergio Alberto Rupp [UNESP] Zornoff, Leonardo Antonio Mamede [UNESP] Okoshi, Marina Politi [UNESP] Matsubara, Beatriz Bojikian [UNESP] Matsubara, Luiz Shiguero [UNESP] |
author_role |
author |
author2 |
Minicucci, Marcos Ferreira [UNESP] Azevedo, Paula Schmidt [UNESP] Carvalho, Robson Francisco [UNESP] Chiuso-Minicucci, Fernanda [UNESP] Pereira, Elenize Jamas [UNESP] Paiva, Sergio Alberto Rupp [UNESP] Zornoff, Leonardo Antonio Mamede [UNESP] Okoshi, Marina Politi [UNESP] Matsubara, Beatriz Bojikian [UNESP] Matsubara, Luiz Shiguero [UNESP] |
author2_role |
author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Polegato, Bertha Furlan [UNESP] Minicucci, Marcos Ferreira [UNESP] Azevedo, Paula Schmidt [UNESP] Carvalho, Robson Francisco [UNESP] Chiuso-Minicucci, Fernanda [UNESP] Pereira, Elenize Jamas [UNESP] Paiva, Sergio Alberto Rupp [UNESP] Zornoff, Leonardo Antonio Mamede [UNESP] Okoshi, Marina Politi [UNESP] Matsubara, Beatriz Bojikian [UNESP] Matsubara, Luiz Shiguero [UNESP] |
dc.subject.por.fl_str_mv |
Isolated heart study Cytokines Phospholamban Ryanodine receptor Serca-2a Matrix metalloproteinase Doxorubicin Acute cardiotoxicity |
topic |
Isolated heart study Cytokines Phospholamban Ryanodine receptor Serca-2a Matrix metalloproteinase Doxorubicin Acute cardiotoxicity |
description |
Background: Doxorubicin can cause cardiotoxicity. Matrix metalloproteinases (MMP) are responsible for degrading extracellular matrix components which play a role in ventricular dilation. Increased MMP activity occurs after chronic doxorubicin treatment. In this study we evaluated in vivo and in vitro cardiac function in rats with acute doxorubicin treatment, and examined myocardial MMP and inflammatory activation, and gene expression of proteins involved in myocyte calcium transients. Methods: Wistar rats were injected with doxorubicin (Doxo, 20 mg/kg) or saline (Control). Echocardiogram was performed 48 h after treatment. Myocardial function was assessed in vitro in Langendorff preparation. Results: In left ventricle, doxorubicin impaired fractional shortening (Control 0.59 +/- 0.07; Doxo 0.51 +/- 0.05; p < 0.001), and increased isovolumetric relaxation time (Control 20.3 +/- 4.3; Doxo 24.7 +/- 4.2 ms; p = 0.007) and myocardial passive stiffness. MMP-2 activity, evaluated by zymography, was increased in Doxo (Control 141338 +/- 8924; Doxo 188874 +/- 7652 arbitrary units; p < 0.001). There were no changes in TNF-alpha, INF-gamma, IL-10, and ICAM-1 myocardial levels. Expression of phospholamban, Serca-2a, and ryanodine receptor did not differ between groups. Conclusion: Acute doxorubicin administration induces in vivo left ventricular dysfunction and in vitro increased myocardial passive stiffness in rats. Cardiac dysfunction is related to myocardial MMP-2 activation. Increased inflammatory stimulation or changed expression of the proteins involved in intracellular calcium transients is not involved in acute cardiac dysfunction. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-10-21T13:08:55Z 2015-10-21T13:08:55Z 2015-01-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://www.karger.com/Article/FullText/374001 Cellular Physiology And Biochemistry. Basel: Karger, v. 35, n. 5, p. 1924-1933, 2015. 1015-8987 http://hdl.handle.net/11449/128314 10.1159/000374001 WOS:000353713900022 WOS000353713900022.pdf 5406518799128485 6990977122340795 4463138671998432 6309835137998766 5016839015394547 1213140801402647 7438704034471673 0000-0002-4901-7714 0000-0002-9831-8820 0000-0002-5843-6232 |
url |
http://www.karger.com/Article/FullText/374001 http://hdl.handle.net/11449/128314 |
identifier_str_mv |
Cellular Physiology And Biochemistry. Basel: Karger, v. 35, n. 5, p. 1924-1933, 2015. 1015-8987 10.1159/000374001 WOS:000353713900022 WOS000353713900022.pdf 5406518799128485 6990977122340795 4463138671998432 6309835137998766 5016839015394547 1213140801402647 7438704034471673 0000-0002-4901-7714 0000-0002-9831-8820 0000-0002-5843-6232 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Cellular Physiology And Biochemistry 5.500 1,561 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
1924-1933 application/pdf |
dc.publisher.none.fl_str_mv |
Karger |
publisher.none.fl_str_mv |
Karger |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808128114557976576 |