Cell therapy prevents structural, functional and molecular remodeling of remote non-infarcted myocardium

Cell therapy prevents structural, functional and molecular remodeling of remote non-infarcted myocardium

Author Santos, Leonardo dos Autor UNIFESP Google Scholar
Gonçalves, Giovana Aparecida Autor UNIFESP Google Scholar
Davel, Ana Paula Google Scholar
Santos, Alexandra Alberta dos Autor UNIFESP Google Scholar
Krieger, Jose Eduardo Google Scholar
Rossoni, Luciana Venturini Google Scholar
Tucci, Paulo José Ferreira Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade Estadual de Campinas (UNICAMP)
Universidade de São Paulo (USP)
Abstract 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.
Keywords Myocardial remodeling
Stem-cell
Calcium-handling
Capillary
Hypertrophy
Language English
Sponsor Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Date 2013-10-09
Published in International Journal of Cardiology. Clare: Elsevier B.V., v. 168, n. 4, p. 3829-3836, 2013.
ISSN 0167-5273 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 3829-3836
Origin http://dx.doi.org/10.1016/j.ijcard.2013.06.026
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000326219600112
URI http://repositorio.unifesp.br/handle/11600/36871

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