Methotrexate associated to lipid core nanoparticles improves cardiac allograft vasculopathy and the inflammatory profile in a rabbit heart graft model
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Brazilian Journal of Medical and Biological Research |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2017001000608 |
Resumo: | Coronary allograft vasculopathy is an inflammatory-proliferative process that compromises the long-term success of heart transplantation and has no effective treatment. A lipid nanoemulsion (LDE) can carry chemotherapeutic agents in the circulation and concentrates them in the heart graft. The aim of the study was to investigate the effects of methotrexate (MTX) associated to LDE. Rabbits fed a 0.5% cholesterol diet and submitted to heterotopic heart transplantation were treated with cyclosporine A (10 mg·kg–1·day–1 orally) and allocated to treatment with intravenous LDE-MTX (4 mg/kg, weekly, n=10) or with weekly intravenous saline solution (control group, n=10), beginning on the day of surgery. Animals were euthanized 6 weeks later. Compared to controls, grafts of LDE-MTX treated rabbits showed 20% reduction of coronary stenosis, with a four-fold increase in vessel lumen and 80% reduction of macrophage staining in grafts. Necrosis was attenuated by LDE-MTX. Native hearts of both LDE-MTX and Control groups were apparently normal. Gene expression of lipoprotein receptors was significantly greater in grafts compared to native hearts. In LDE-MTX group, gene expression of the pro-inflammatory factors tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-18, vascular cell adhesion molecule-1, and matrix metalloproteinase-12 was strongly diminished whereas expression of anti-inflammatory interleukin-10 increased. LDE-MTX promoted improvement of the cardiac allograft vasculopathy and diminished inflammation in heart grafts. |
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Brazilian Journal of Medical and Biological Research |
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Methotrexate associated to lipid core nanoparticles improves cardiac allograft vasculopathy and the inflammatory profile in a rabbit heart graft modelNanoemulsionsSolid lipid particlesMethotrexateInflammatory mediatorsLDL receptorsCoronary allograft vasculopathy is an inflammatory-proliferative process that compromises the long-term success of heart transplantation and has no effective treatment. A lipid nanoemulsion (LDE) can carry chemotherapeutic agents in the circulation and concentrates them in the heart graft. The aim of the study was to investigate the effects of methotrexate (MTX) associated to LDE. Rabbits fed a 0.5% cholesterol diet and submitted to heterotopic heart transplantation were treated with cyclosporine A (10 mg·kg–1·day–1 orally) and allocated to treatment with intravenous LDE-MTX (4 mg/kg, weekly, n=10) or with weekly intravenous saline solution (control group, n=10), beginning on the day of surgery. Animals were euthanized 6 weeks later. Compared to controls, grafts of LDE-MTX treated rabbits showed 20% reduction of coronary stenosis, with a four-fold increase in vessel lumen and 80% reduction of macrophage staining in grafts. Necrosis was attenuated by LDE-MTX. Native hearts of both LDE-MTX and Control groups were apparently normal. Gene expression of lipoprotein receptors was significantly greater in grafts compared to native hearts. In LDE-MTX group, gene expression of the pro-inflammatory factors tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-18, vascular cell adhesion molecule-1, and matrix metalloproteinase-12 was strongly diminished whereas expression of anti-inflammatory interleukin-10 increased. LDE-MTX promoted improvement of the cardiac allograft vasculopathy and diminished inflammation in heart grafts.Associação Brasileira de Divulgação Científica2017-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2017001000608Brazilian Journal of Medical and Biological Research v.50 n.10 2017reponame:Brazilian Journal of Medical and Biological Researchinstname:Associação Brasileira de Divulgação Científica (ABDC)instacron:ABDC10.1590/1414-431x20176225info:eu-repo/semantics/openAccessFiorelli,A.I.Lourenço-Filho,D.D.Tavares,E.R.Carvalho,P.O.Marques,A.F.Gutierrez,P.S.Maranhão,R.C.Stolf,N.A.G.eng2019-03-19T00:00:00Zoai:scielo:S0100-879X2017001000608Revistahttps://www.bjournal.org/https://old.scielo.br/oai/scielo-oai.phpbjournal@terra.com.br||bjournal@terra.com.br1414-431X0100-879Xopendoar:2019-03-19T00:00Brazilian Journal of Medical and Biological Research - Associação Brasileira de Divulgação Científica (ABDC)false |
dc.title.none.fl_str_mv |
Methotrexate associated to lipid core nanoparticles improves cardiac allograft vasculopathy and the inflammatory profile in a rabbit heart graft model |
title |
Methotrexate associated to lipid core nanoparticles improves cardiac allograft vasculopathy and the inflammatory profile in a rabbit heart graft model |
spellingShingle |
Methotrexate associated to lipid core nanoparticles improves cardiac allograft vasculopathy and the inflammatory profile in a rabbit heart graft model Fiorelli,A.I. Nanoemulsions Solid lipid particles Methotrexate Inflammatory mediators LDL receptors |
title_short |
Methotrexate associated to lipid core nanoparticles improves cardiac allograft vasculopathy and the inflammatory profile in a rabbit heart graft model |
title_full |
Methotrexate associated to lipid core nanoparticles improves cardiac allograft vasculopathy and the inflammatory profile in a rabbit heart graft model |
title_fullStr |
Methotrexate associated to lipid core nanoparticles improves cardiac allograft vasculopathy and the inflammatory profile in a rabbit heart graft model |
title_full_unstemmed |
Methotrexate associated to lipid core nanoparticles improves cardiac allograft vasculopathy and the inflammatory profile in a rabbit heart graft model |
title_sort |
Methotrexate associated to lipid core nanoparticles improves cardiac allograft vasculopathy and the inflammatory profile in a rabbit heart graft model |
author |
Fiorelli,A.I. |
author_facet |
Fiorelli,A.I. Lourenço-Filho,D.D. Tavares,E.R. Carvalho,P.O. Marques,A.F. Gutierrez,P.S. Maranhão,R.C. Stolf,N.A.G. |
author_role |
author |
author2 |
Lourenço-Filho,D.D. Tavares,E.R. Carvalho,P.O. Marques,A.F. Gutierrez,P.S. Maranhão,R.C. Stolf,N.A.G. |
author2_role |
author author author author author author author |
dc.contributor.author.fl_str_mv |
Fiorelli,A.I. Lourenço-Filho,D.D. Tavares,E.R. Carvalho,P.O. Marques,A.F. Gutierrez,P.S. Maranhão,R.C. Stolf,N.A.G. |
dc.subject.por.fl_str_mv |
Nanoemulsions Solid lipid particles Methotrexate Inflammatory mediators LDL receptors |
topic |
Nanoemulsions Solid lipid particles Methotrexate Inflammatory mediators LDL receptors |
description |
Coronary allograft vasculopathy is an inflammatory-proliferative process that compromises the long-term success of heart transplantation and has no effective treatment. A lipid nanoemulsion (LDE) can carry chemotherapeutic agents in the circulation and concentrates them in the heart graft. The aim of the study was to investigate the effects of methotrexate (MTX) associated to LDE. Rabbits fed a 0.5% cholesterol diet and submitted to heterotopic heart transplantation were treated with cyclosporine A (10 mg·kg–1·day–1 orally) and allocated to treatment with intravenous LDE-MTX (4 mg/kg, weekly, n=10) or with weekly intravenous saline solution (control group, n=10), beginning on the day of surgery. Animals were euthanized 6 weeks later. Compared to controls, grafts of LDE-MTX treated rabbits showed 20% reduction of coronary stenosis, with a four-fold increase in vessel lumen and 80% reduction of macrophage staining in grafts. Necrosis was attenuated by LDE-MTX. Native hearts of both LDE-MTX and Control groups were apparently normal. Gene expression of lipoprotein receptors was significantly greater in grafts compared to native hearts. In LDE-MTX group, gene expression of the pro-inflammatory factors tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-18, vascular cell adhesion molecule-1, and matrix metalloproteinase-12 was strongly diminished whereas expression of anti-inflammatory interleukin-10 increased. LDE-MTX promoted improvement of the cardiac allograft vasculopathy and diminished inflammation in heart grafts. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-01-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2017001000608 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2017001000608 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/1414-431x20176225 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Associação Brasileira de Divulgação Científica |
publisher.none.fl_str_mv |
Associação Brasileira de Divulgação Científica |
dc.source.none.fl_str_mv |
Brazilian Journal of Medical and Biological Research v.50 n.10 2017 reponame:Brazilian Journal of Medical and Biological Research instname:Associação Brasileira de Divulgação Científica (ABDC) instacron:ABDC |
instname_str |
Associação Brasileira de Divulgação Científica (ABDC) |
instacron_str |
ABDC |
institution |
ABDC |
reponame_str |
Brazilian Journal of Medical and Biological Research |
collection |
Brazilian Journal of Medical and Biological Research |
repository.name.fl_str_mv |
Brazilian Journal of Medical and Biological Research - Associação Brasileira de Divulgação Científica (ABDC) |
repository.mail.fl_str_mv |
bjournal@terra.com.br||bjournal@terra.com.br |
_version_ |
1754302945871003648 |