Efeitos da Angiotensina-(1-7) na inflamação e reparo tecidual
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFU |
Texto Completo: | https://repositorio.ufu.br/handle/123456789/19622 https://doi.org/10.14393/ufu.te.2014.78 |
Resumo: | Background: (Ang-(1-7)), a bioactive heptapeptide formed from the fragmentation of angiotensin I and acts as an antagonist of angiotensin II and carries anti angiogenic, antifibrotic, antiproliferative properties. However, the effects of this peptide on the development of fibroproliferative tissue induced by synthetic sponge matrix has not been fully characterized. Methods: Male Swiss mice (7-8 weeks) were implanted subcutaneously with polyether-polyurethane sponge discs for induction of the fibrovascular tissue. Ang-(1-7) treatment (30ng) was carried out by intraimplant daily administration. Implants collected 1, 4, 7, 9 and 14 days postimplantation were analyzed for determination of angiogenesis (hemoglobin (Hb), blood vessels number and levels of pro-angiogenic cytokines (VEGF and bFGF), inflammation (myeloperoxidase- MPO and N-acetyl-P-D-glucosaminidase-NAG activities and levels of pro-inflammatory cytokines -TNF-a, CXCL1/KC and CCL2) and fibrogenesis (collagen deposition and TGFP-1 levels). Results: Ang-(1-7) exerted dual effects of the development of neovascularization in the sponge implants as assessed by measuring Hb content and number of vessels. At days 4 and 7 the peptide inhibited increases of these parameters when compared with the non-treated group. From day 9 onwards, the peptide increased hemoglobin (42%), vessel number (46%), FGF (24%) and VEGF level (29%) relative to the control group. This pattern was also observed for the inflammatory marker and cytokine production. The Ang-(1-7) treatment was able to decreased CXCL1 (48%), TNF-a (25%), NAG (58%), CCL2 (32%) from day 1 and MPO (27%) from day 3 relative to the control group. This pattern changed relative to tissue repair in sponge implants. Total soluble collagen (105%), collagen content (37%) and TGF-P1(50%) were increased after 7 days of treatment with Ang-(1-7). During these 14 days there was involvement of processes of fibrosis and tissue remodeling, as shown by mast cells number that were greater than control group (32%)(p<0.05).Conclusion: After 14 days of treatment the inhibitory effect of Ang-(1-7) to attenuate inflammation and promote angiogenesis and fibrogenic components of the fibrovascular tissue induced by the synthetic matrix extends the range of actions of the Ang-(1-7) and may indicate its therapeutic potential in controlling diseases. |
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Efeitos da Angiotensina-(1-7) na inflamação e reparo tecidualGenéticaAngiotensinasInflamaçãoNeovascularizaçãoAngiotensina- (1-7)AngiogêneseFibroseImplantesEsponjaAngiotensin-(1-7)AngiogenesisInflammationFibrosisImplantsSponge discCNPQ::CIENCIAS BIOLOGICAS::GENETICABackground: (Ang-(1-7)), a bioactive heptapeptide formed from the fragmentation of angiotensin I and acts as an antagonist of angiotensin II and carries anti angiogenic, antifibrotic, antiproliferative properties. However, the effects of this peptide on the development of fibroproliferative tissue induced by synthetic sponge matrix has not been fully characterized. Methods: Male Swiss mice (7-8 weeks) were implanted subcutaneously with polyether-polyurethane sponge discs for induction of the fibrovascular tissue. Ang-(1-7) treatment (30ng) was carried out by intraimplant daily administration. Implants collected 1, 4, 7, 9 and 14 days postimplantation were analyzed for determination of angiogenesis (hemoglobin (Hb), blood vessels number and levels of pro-angiogenic cytokines (VEGF and bFGF), inflammation (myeloperoxidase- MPO and N-acetyl-P-D-glucosaminidase-NAG activities and levels of pro-inflammatory cytokines -TNF-a, CXCL1/KC and CCL2) and fibrogenesis (collagen deposition and TGFP-1 levels). Results: Ang-(1-7) exerted dual effects of the development of neovascularization in the sponge implants as assessed by measuring Hb content and number of vessels. At days 4 and 7 the peptide inhibited increases of these parameters when compared with the non-treated group. From day 9 onwards, the peptide increased hemoglobin (42%), vessel number (46%), FGF (24%) and VEGF level (29%) relative to the control group. This pattern was also observed for the inflammatory marker and cytokine production. The Ang-(1-7) treatment was able to decreased CXCL1 (48%), TNF-a (25%), NAG (58%), CCL2 (32%) from day 1 and MPO (27%) from day 3 relative to the control group. This pattern changed relative to tissue repair in sponge implants. Total soluble collagen (105%), collagen content (37%) and TGF-P1(50%) were increased after 7 days of treatment with Ang-(1-7). During these 14 days there was involvement of processes of fibrosis and tissue remodeling, as shown by mast cells number that were greater than control group (32%)(p<0.05).Conclusion: After 14 days of treatment the inhibitory effect of Ang-(1-7) to attenuate inflammation and promote angiogenesis and fibrogenic components of the fibrovascular tissue induced by the synthetic matrix extends the range of actions of the Ang-(1-7) and may indicate its therapeutic potential in controlling diseases.Tese (Doutorado)Angiotensina-(1-7) (Ang- (1-7)), é um heptapeptídeo bioativo com propriedades antiangiogênicas, antifibróticas e antiproliferativas. No entanto, os efeitos deste peptídeo no desenvolvimento de tecido fibroproliferativo induzido por matriz de esponja sintética ainda não foram completamente caracterizados. Metodologia: camundongos machos swiss (7-8 semanas) receberam como implantes discos de esponja de poliéster-poliuretano para indução de tecido fibrovascular. O tratamento com Ang- (1-7) (30 ng) foi realizado por administração diária intraimplante. Para determinação da angiogênese foi avaliado o conteúdo de hemoglobina (Hb), número de vasos sanguíneos e níveis de citocinas pró-angiogênicas (VEGF e bFGF). Para os fatores inflamatórios foram dosadas mieloperoxidase-MPO, N-acetil -P-D-glucosaminidase-NAG, níveis de citocinas pró-inflamatórias -TNF-a, CXCL1 / KC e CCL2). A fibrogênese foi analisada de acordo com a deposição de colágeno e níveis de TGFP-1. Todas as análises foram analisadas a partir dos implantes coletados nos dias 1, 4, 7, 9 e 14 pós-implantação. Resultados: Ang- (1-7) exerceu duplo efeito no desenvolvimento da neovascularização dos implantes de esponja, avaliado pela medição do conteúdo de Hb e do número de vasos. Nos dias 4 e 7 o peptídeo inibiu os aumentos desses parâmetros quando comparados com o grupo não tratado. Do dia 9 em diante, o péptideo aumentou os níveis de Hb (42%), número de vaso (46%), FGF (24%) e nível de VEGF (29%) em relação ao grupo controle. Esse padrão também foi observado para o marcador inflamatório e a produção de citoquinas. O tratamento com a Ang- (1- 7) foi capaz de diminuir CXCL1 (48%), TNF-a (25%), NAG (58%), CC L2 (32%) do dia 1 e MPO (27%) a partir do dia 3 em relação ao grupo controle. Este padrão mudou em relação ao reparo do tecido em implantes de esponja. O colágeno solúvel total (105%), o teor de colágeno (37%) e o TGF-pi (50%) aumentaram após 7 dias de tratamento com Ang- (17). Durante esses 14 dias, processos fibróticos e de remodelação tecidual foram envolvidos, como mostrado pelo aumento de mastócitos em relação ao grupo controle (32%) (p <0,05). Conclusão: após 14 dias de tratamento, o efeito inibitório da Ang- (17) na atenuação da inflamação e promoção da angiogênese e componentes fibrogênicos do tecido fibrovascular induzido pela matriz sintética se estende ao alcance das ações da Ang- (1-7) podendo indicar potencial terapêutico no controle de doenças.Universidade Federal de UberlândiaBrasilPrograma de Pós-graduação em Genética e BioquímicaAraújo, Fernanda de Assishttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4710930P1Oliveira, Fábio dehttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4799971D5Silva, Cláudio Vieira dahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4704340J2Ribeiro, Daniele Lisboahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4773409A6Clissa, Patricia Biancahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4728679U1Moura, Sandra Aparecida Lima dehttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4779623U6Deconte, Simone Ramos2017-08-29T13:09:55Z2017-08-29T13:09:55Z2014-07-28info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfDECONTE, Simone Ramos. Efeitos da Angiotensina-(1-7) na inflamação e reparo tecidual. 2017. 95 f. Tese (Doutorado em Genética e Bioquímica) - Universidade Federal de Uberlândia, Uberlândia, 2017. DOI https://doi.org/10.14393/ufu.te.2014.78https://repositorio.ufu.br/handle/123456789/19622https://doi.org/10.14393/ufu.te.2014.78porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFUinstname:Universidade Federal de Uberlândia (UFU)instacron:UFU2021-07-23T21:57:09Zoai:repositorio.ufu.br:123456789/19622Repositório InstitucionalONGhttp://repositorio.ufu.br/oai/requestdiinf@dirbi.ufu.bropendoar:2021-07-23T21:57:09Repositório Institucional da UFU - Universidade Federal de Uberlândia (UFU)false |
dc.title.none.fl_str_mv |
Efeitos da Angiotensina-(1-7) na inflamação e reparo tecidual |
title |
Efeitos da Angiotensina-(1-7) na inflamação e reparo tecidual |
spellingShingle |
Efeitos da Angiotensina-(1-7) na inflamação e reparo tecidual Deconte, Simone Ramos Genética Angiotensinas Inflamação Neovascularização Angiotensina- (1-7) Angiogênese Fibrose Implantes Esponja Angiotensin-(1-7) Angiogenesis Inflammation Fibrosis Implants Sponge disc CNPQ::CIENCIAS BIOLOGICAS::GENETICA |
title_short |
Efeitos da Angiotensina-(1-7) na inflamação e reparo tecidual |
title_full |
Efeitos da Angiotensina-(1-7) na inflamação e reparo tecidual |
title_fullStr |
Efeitos da Angiotensina-(1-7) na inflamação e reparo tecidual |
title_full_unstemmed |
Efeitos da Angiotensina-(1-7) na inflamação e reparo tecidual |
title_sort |
Efeitos da Angiotensina-(1-7) na inflamação e reparo tecidual |
author |
Deconte, Simone Ramos |
author_facet |
Deconte, Simone Ramos |
author_role |
author |
dc.contributor.none.fl_str_mv |
Araújo, Fernanda de Assis http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4710930P1 Oliveira, Fábio de http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4799971D5 Silva, Cláudio Vieira da http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4704340J2 Ribeiro, Daniele Lisboa http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4773409A6 Clissa, Patricia Bianca http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4728679U1 Moura, Sandra Aparecida Lima de http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4779623U6 |
dc.contributor.author.fl_str_mv |
Deconte, Simone Ramos |
dc.subject.por.fl_str_mv |
Genética Angiotensinas Inflamação Neovascularização Angiotensina- (1-7) Angiogênese Fibrose Implantes Esponja Angiotensin-(1-7) Angiogenesis Inflammation Fibrosis Implants Sponge disc CNPQ::CIENCIAS BIOLOGICAS::GENETICA |
topic |
Genética Angiotensinas Inflamação Neovascularização Angiotensina- (1-7) Angiogênese Fibrose Implantes Esponja Angiotensin-(1-7) Angiogenesis Inflammation Fibrosis Implants Sponge disc CNPQ::CIENCIAS BIOLOGICAS::GENETICA |
description |
Background: (Ang-(1-7)), a bioactive heptapeptide formed from the fragmentation of angiotensin I and acts as an antagonist of angiotensin II and carries anti angiogenic, antifibrotic, antiproliferative properties. However, the effects of this peptide on the development of fibroproliferative tissue induced by synthetic sponge matrix has not been fully characterized. Methods: Male Swiss mice (7-8 weeks) were implanted subcutaneously with polyether-polyurethane sponge discs for induction of the fibrovascular tissue. Ang-(1-7) treatment (30ng) was carried out by intraimplant daily administration. Implants collected 1, 4, 7, 9 and 14 days postimplantation were analyzed for determination of angiogenesis (hemoglobin (Hb), blood vessels number and levels of pro-angiogenic cytokines (VEGF and bFGF), inflammation (myeloperoxidase- MPO and N-acetyl-P-D-glucosaminidase-NAG activities and levels of pro-inflammatory cytokines -TNF-a, CXCL1/KC and CCL2) and fibrogenesis (collagen deposition and TGFP-1 levels). Results: Ang-(1-7) exerted dual effects of the development of neovascularization in the sponge implants as assessed by measuring Hb content and number of vessels. At days 4 and 7 the peptide inhibited increases of these parameters when compared with the non-treated group. From day 9 onwards, the peptide increased hemoglobin (42%), vessel number (46%), FGF (24%) and VEGF level (29%) relative to the control group. This pattern was also observed for the inflammatory marker and cytokine production. The Ang-(1-7) treatment was able to decreased CXCL1 (48%), TNF-a (25%), NAG (58%), CCL2 (32%) from day 1 and MPO (27%) from day 3 relative to the control group. This pattern changed relative to tissue repair in sponge implants. Total soluble collagen (105%), collagen content (37%) and TGF-P1(50%) were increased after 7 days of treatment with Ang-(1-7). During these 14 days there was involvement of processes of fibrosis and tissue remodeling, as shown by mast cells number that were greater than control group (32%)(p<0.05).Conclusion: After 14 days of treatment the inhibitory effect of Ang-(1-7) to attenuate inflammation and promote angiogenesis and fibrogenic components of the fibrovascular tissue induced by the synthetic matrix extends the range of actions of the Ang-(1-7) and may indicate its therapeutic potential in controlling diseases. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-07-28 2017-08-29T13:09:55Z 2017-08-29T13:09:55Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
DECONTE, Simone Ramos. Efeitos da Angiotensina-(1-7) na inflamação e reparo tecidual. 2017. 95 f. Tese (Doutorado em Genética e Bioquímica) - Universidade Federal de Uberlândia, Uberlândia, 2017. DOI https://doi.org/10.14393/ufu.te.2014.78 https://repositorio.ufu.br/handle/123456789/19622 https://doi.org/10.14393/ufu.te.2014.78 |
identifier_str_mv |
DECONTE, Simone Ramos. Efeitos da Angiotensina-(1-7) na inflamação e reparo tecidual. 2017. 95 f. Tese (Doutorado em Genética e Bioquímica) - Universidade Federal de Uberlândia, Uberlândia, 2017. DOI https://doi.org/10.14393/ufu.te.2014.78 |
url |
https://repositorio.ufu.br/handle/123456789/19622 https://doi.org/10.14393/ufu.te.2014.78 |
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por |
language |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Universidade Federal de Uberlândia Brasil Programa de Pós-graduação em Genética e Bioquímica |
publisher.none.fl_str_mv |
Universidade Federal de Uberlândia Brasil Programa de Pós-graduação em Genética e Bioquímica |
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reponame:Repositório Institucional da UFU instname:Universidade Federal de Uberlândia (UFU) instacron:UFU |
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Universidade Federal de Uberlândia (UFU) |
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UFU |
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Repositório Institucional da UFU |
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Repositório Institucional da UFU |
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Repositório Institucional da UFU - Universidade Federal de Uberlândia (UFU) |
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diinf@dirbi.ufu.br |
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