Cell therapy prevents structural, functional and molecular remodeling of remote non-infarcted myocardium
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/36871 http://dx.doi.org/10.1016/j.ijcard.2013.06.026 |
Resumo: | Background/objectives: Therapy using bone marrow (BM) cells has been tested experimentally and clinically due to the potential ability to restore cardiac function by regenerating lost myocytes or increasing the survival of tissues at risk after myocardial infarction (MI). in this study we aimed to evaluate whether BM-derived mononuclear cell (MNC) implantation can positively influence the post-MI structural remodeling, contractility and Ca(2+)-handling proteins of the remote non-infarcted tissue in rats.Methods and results: After 48 h of MI induction, saline or BM-MNC were injected. Six weeks later, MI scars were slightly smaller and thicker, and cardiac dilatation was just partially prevented by cell therapy. However, the cardiac performance under hemodynamic stress was totally preserved in the BM-MNC treated group if compared to the untreated group, associated with normal contractility of remote myocardium as analyzed in vitro. the impaired post-rest potentiation of contractile force, associated with decreased protein expression of the sarcoplasmic reticulum Ca2+-ATPase and phosphorylated-phospholamban and overexpression of Na(+)/Ca(2+) exchanger, were prevented by BM-MNC, indicating preservation of the Ca(2+) handling. Finally, pathological changes on remodeled remote tissue such as myocyte hypertrophy, interstitial fibrosis and capillary rarefaction were also mitigated by cell therapy.Conclusions: BM-MNC therapy was able to prevent cardiac structural and molecular remodeling after MI, avoiding pathological changes on Ca(2+)-handling proteins and preserving contractile behavior of the viable myocardium, which could be the major contributor to the improvements of global cardiac performance after cell transplantation despite that scar tissue still exists. (C) 2013 Elsevier Ireland Ltd. All rights reserved. |
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Santos, Leonardo dos [UNIFESP]Gonçalves, Giovana Aparecida [UNIFESP]Davel, Ana PaulaSantos, Alexandra Alberta dos [UNIFESP]Krieger, Jose EduardoRossoni, Luciana VenturiniTucci, Paulo José Ferreira [UNIFESP]Universidade Federal de São Paulo (UNIFESP)Universidade Estadual de Campinas (UNICAMP)Universidade de São Paulo (USP)2016-01-24T14:34:34Z2016-01-24T14:34:34Z2013-10-09International Journal of Cardiology. Clare: Elsevier B.V., v. 168, n. 4, p. 3829-3836, 2013.0167-5273http://repositorio.unifesp.br/handle/11600/36871http://dx.doi.org/10.1016/j.ijcard.2013.06.026WOS000326219600112.pdf10.1016/j.ijcard.2013.06.026WOS:000326219600112Background/objectives: Therapy using bone marrow (BM) cells has been tested experimentally and clinically due to the potential ability to restore cardiac function by regenerating lost myocytes or increasing the survival of tissues at risk after myocardial infarction (MI). in this study we aimed to evaluate whether BM-derived mononuclear cell (MNC) implantation can positively influence the post-MI structural remodeling, contractility and Ca(2+)-handling proteins of the remote non-infarcted tissue in rats.Methods and results: After 48 h of MI induction, saline or BM-MNC were injected. Six weeks later, MI scars were slightly smaller and thicker, and cardiac dilatation was just partially prevented by cell therapy. However, the cardiac performance under hemodynamic stress was totally preserved in the BM-MNC treated group if compared to the untreated group, associated with normal contractility of remote myocardium as analyzed in vitro. the impaired post-rest potentiation of contractile force, associated with decreased protein expression of the sarcoplasmic reticulum Ca2+-ATPase and phosphorylated-phospholamban and overexpression of Na(+)/Ca(2+) exchanger, were prevented by BM-MNC, indicating preservation of the Ca(2+) handling. Finally, pathological changes on remodeled remote tissue such as myocyte hypertrophy, interstitial fibrosis and capillary rarefaction were also mitigated by cell therapy.Conclusions: BM-MNC therapy was able to prevent cardiac structural and molecular remodeling after MI, avoiding pathological changes on Ca(2+)-handling proteins and preserving contractile behavior of the viable myocardium, which could be the major contributor to the improvements of global cardiac performance after cell transplantation despite that scar tissue still exists. (C) 2013 Elsevier Ireland Ltd. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Med, São Paulo, BrazilUniv Estadual Campinas, Dept Struct & Funct Biol, Campinas, SP, BrazilUniv São Paulo, Inst Heart, BR-05508 São Paulo, BrazilUniv São Paulo, Inst Biomed Sci, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, São Paulo, BrazilWeb of Science3829-3836engElsevier B.V.International Journal of Cardiologyhttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policyinfo:eu-repo/semantics/openAccessMyocardial remodelingStem-cellCalcium-handlingCapillaryHypertrophyCell therapy prevents structural, functional and molecular remodeling of remote non-infarcted myocardiuminfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlereponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000326219600112.pdfapplication/pdf1339207${dspace.ui.url}/bitstream/11600/36871/1/WOS000326219600112.pdf5808f6c8029a2618604e40d2aeb8f3b7MD51open accessTEXTWOS000326219600112.pdf.txtWOS000326219600112.pdf.txtExtracted texttext/plain43848${dspace.ui.url}/bitstream/11600/36871/2/WOS000326219600112.pdf.txt2621e15b39f3e3295d00c1eeef33f4d7MD52open access11600/368712023-01-30 22:17:46.749open accessoai:repositorio.unifesp.br:11600/36871Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-01-31T01:17:46Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Cell therapy prevents structural, functional and molecular remodeling of remote non-infarcted myocardium |
title |
Cell therapy prevents structural, functional and molecular remodeling of remote non-infarcted myocardium |
spellingShingle |
Cell therapy prevents structural, functional and molecular remodeling of remote non-infarcted myocardium Santos, Leonardo dos [UNIFESP] Myocardial remodeling Stem-cell Calcium-handling Capillary Hypertrophy |
title_short |
Cell therapy prevents structural, functional and molecular remodeling of remote non-infarcted myocardium |
title_full |
Cell therapy prevents structural, functional and molecular remodeling of remote non-infarcted myocardium |
title_fullStr |
Cell therapy prevents structural, functional and molecular remodeling of remote non-infarcted myocardium |
title_full_unstemmed |
Cell therapy prevents structural, functional and molecular remodeling of remote non-infarcted myocardium |
title_sort |
Cell therapy prevents structural, functional and molecular remodeling of remote non-infarcted myocardium |
author |
Santos, Leonardo dos [UNIFESP] |
author_facet |
Santos, Leonardo dos [UNIFESP] Gonçalves, Giovana Aparecida [UNIFESP] Davel, Ana Paula Santos, Alexandra Alberta dos [UNIFESP] Krieger, Jose Eduardo Rossoni, Luciana Venturini Tucci, Paulo José Ferreira [UNIFESP] |
author_role |
author |
author2 |
Gonçalves, Giovana Aparecida [UNIFESP] Davel, Ana Paula Santos, Alexandra Alberta dos [UNIFESP] Krieger, Jose Eduardo Rossoni, Luciana Venturini Tucci, Paulo José Ferreira [UNIFESP] |
author2_role |
author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) Universidade Estadual de Campinas (UNICAMP) Universidade de São Paulo (USP) |
dc.contributor.author.fl_str_mv |
Santos, Leonardo dos [UNIFESP] Gonçalves, Giovana Aparecida [UNIFESP] Davel, Ana Paula Santos, Alexandra Alberta dos [UNIFESP] Krieger, Jose Eduardo Rossoni, Luciana Venturini Tucci, Paulo José Ferreira [UNIFESP] |
dc.subject.eng.fl_str_mv |
Myocardial remodeling Stem-cell Calcium-handling Capillary Hypertrophy |
topic |
Myocardial remodeling Stem-cell Calcium-handling Capillary Hypertrophy |
description |
Background/objectives: Therapy using bone marrow (BM) cells has been tested experimentally and clinically due to the potential ability to restore cardiac function by regenerating lost myocytes or increasing the survival of tissues at risk after myocardial infarction (MI). in this study we aimed to evaluate whether BM-derived mononuclear cell (MNC) implantation can positively influence the post-MI structural remodeling, contractility and Ca(2+)-handling proteins of the remote non-infarcted tissue in rats.Methods and results: After 48 h of MI induction, saline or BM-MNC were injected. Six weeks later, MI scars were slightly smaller and thicker, and cardiac dilatation was just partially prevented by cell therapy. However, the cardiac performance under hemodynamic stress was totally preserved in the BM-MNC treated group if compared to the untreated group, associated with normal contractility of remote myocardium as analyzed in vitro. the impaired post-rest potentiation of contractile force, associated with decreased protein expression of the sarcoplasmic reticulum Ca2+-ATPase and phosphorylated-phospholamban and overexpression of Na(+)/Ca(2+) exchanger, were prevented by BM-MNC, indicating preservation of the Ca(2+) handling. Finally, pathological changes on remodeled remote tissue such as myocyte hypertrophy, interstitial fibrosis and capillary rarefaction were also mitigated by cell therapy.Conclusions: BM-MNC therapy was able to prevent cardiac structural and molecular remodeling after MI, avoiding pathological changes on Ca(2+)-handling proteins and preserving contractile behavior of the viable myocardium, which could be the major contributor to the improvements of global cardiac performance after cell transplantation despite that scar tissue still exists. (C) 2013 Elsevier Ireland Ltd. All rights reserved. |
publishDate |
2013 |
dc.date.issued.fl_str_mv |
2013-10-09 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:34:34Z |
dc.date.available.fl_str_mv |
2016-01-24T14:34:34Z |
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.citation.fl_str_mv |
International Journal of Cardiology. Clare: Elsevier B.V., v. 168, n. 4, p. 3829-3836, 2013. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/36871 http://dx.doi.org/10.1016/j.ijcard.2013.06.026 |
dc.identifier.issn.none.fl_str_mv |
0167-5273 |
dc.identifier.file.none.fl_str_mv |
WOS000326219600112.pdf |
dc.identifier.doi.none.fl_str_mv |
10.1016/j.ijcard.2013.06.026 |
dc.identifier.wos.none.fl_str_mv |
WOS:000326219600112 |
identifier_str_mv |
International Journal of Cardiology. Clare: Elsevier B.V., v. 168, n. 4, p. 3829-3836, 2013. 0167-5273 WOS000326219600112.pdf 10.1016/j.ijcard.2013.06.026 WOS:000326219600112 |
url |
http://repositorio.unifesp.br/handle/11600/36871 http://dx.doi.org/10.1016/j.ijcard.2013.06.026 |
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eng |
language |
eng |
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International Journal of Cardiology |
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http://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy info:eu-repo/semantics/openAccess |
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http://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy |
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openAccess |
dc.format.none.fl_str_mv |
3829-3836 |
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Elsevier B.V. |
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Elsevier B.V. |
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