Caracterização do efeito do tecido adiposo perivascular (PVAT) em aortas de camundongos submetidos a sepse aguda

Detalhes bibliográficos
Ano de defesa: 2020
Autor(a) principal: Naiara de Assis Rabelo Ribeiro
Orientador(a): Não Informado pela instituição
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal de Minas Gerais
Brasil
ICB - DEPARTAMENTO DE FARMACOLOGIA
Programa de Pós-Graduação em Ciências Biológicas - Fisiologia e Farmacologia
UFMG
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
COX
Link de acesso: http://hdl.handle.net/1843/35058
Resumo: Perivascular adipose tissue (PVAT) lines the adventitial layer and surrounds most blood vessels. PVAT releases biologically active molecules that regulate vascular tone. Knowing the importance of this tissue in the control of vascular tone and that the systemic hypotension, generated in a case of sepsis, is the main cause of death, this study aimed to study the vasoactive and inflammatory effects of PVAT on aortic hyporeactivity induced by acute sepsis. For this purpose, male Balb / c mice (8 weeks) were used, which were divided into two groups: sham and septic. In the septic group, sepsis was induced by ligation and transverse perforation of the cecum with a 26G needle. In the sham group, the transverse perforation step of the cecum was not performed. 6 hours after sepsis induction, the role of PVAT in vascular tone was assessed in thoracic aortas of the sham and septic groups. Our results demonstrate that although the sham and septic groups have 100% survival, the septic group presented leukopenia marked by neutropenia, hypothermia, arterial hypotension, and a high clinical score when compared to the sham group. Phenylephrine-induced vasoconstriction was significantly reduced in the septic group compared to the sham group in the absence of PVAT. However, in the presence of PVAT, the impairment of vascular contractility observed in the septic group was reestablished. In other words, PVAT presented a vasoconstrictor profile, in contrast to the hyporeactivity caused by sepsis. Among the mechanisms involved in this process, we suggest a reciprocal regulation between reactive oxygen species, in this case, superoxide anion, probably generated from the NADPH oxidase complex, and that by a self-perpetuating cascade, COX-2 and its vasocontractable derivatives, as thromboxane A2 and prostaglandin F2α also act "feeding" this pathway. Therefore, we suggest that the contractile profile presented by PVAT in acute sepsis (6h) is mainly due to the participation of superoxide anions, in addition to derivatives of COX-2 and that both “feed” the cycle favoring the observed contraction.
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spelling Caracterização do efeito do tecido adiposo perivascular (PVAT) em aortas de camundongos submetidos a sepse agudaPVATSepseHiporreatividadeCOXEstresse oxidativoTecido adiposoVasos sanguíneosAortaSepseCiclo-oxigenase 2Estresse oxidativoPerivascular adipose tissue (PVAT) lines the adventitial layer and surrounds most blood vessels. PVAT releases biologically active molecules that regulate vascular tone. Knowing the importance of this tissue in the control of vascular tone and that the systemic hypotension, generated in a case of sepsis, is the main cause of death, this study aimed to study the vasoactive and inflammatory effects of PVAT on aortic hyporeactivity induced by acute sepsis. For this purpose, male Balb / c mice (8 weeks) were used, which were divided into two groups: sham and septic. In the septic group, sepsis was induced by ligation and transverse perforation of the cecum with a 26G needle. In the sham group, the transverse perforation step of the cecum was not performed. 6 hours after sepsis induction, the role of PVAT in vascular tone was assessed in thoracic aortas of the sham and septic groups. Our results demonstrate that although the sham and septic groups have 100% survival, the septic group presented leukopenia marked by neutropenia, hypothermia, arterial hypotension, and a high clinical score when compared to the sham group. Phenylephrine-induced vasoconstriction was significantly reduced in the septic group compared to the sham group in the absence of PVAT. However, in the presence of PVAT, the impairment of vascular contractility observed in the septic group was reestablished. In other words, PVAT presented a vasoconstrictor profile, in contrast to the hyporeactivity caused by sepsis. Among the mechanisms involved in this process, we suggest a reciprocal regulation between reactive oxygen species, in this case, superoxide anion, probably generated from the NADPH oxidase complex, and that by a self-perpetuating cascade, COX-2 and its vasocontractable derivatives, as thromboxane A2 and prostaglandin F2α also act "feeding" this pathway. Therefore, we suggest that the contractile profile presented by PVAT in acute sepsis (6h) is mainly due to the participation of superoxide anions, in addition to derivatives of COX-2 and that both “feed” the cycle favoring the observed contraction.O tecido adiposo perivascular (PVAT) reveste a camada adventícia e envolve a maioria dos vasos sanguíneos. O PVAT libera moléculas biologicamente ativas que regulam o tônus vascular. Sabendo da importância desse tecido no controle do tônus vascular e que a hipotensão sistêmica, gerada em um quadro de sepse, é a principal causa de morte, o objetivo desse trabalho foi estudar os efeitos vasoativos e inflamatórios do PVAT na hiporreatividade aórtica induzida por sepse aguda. Para tanto, utilizou-se camundongos Balb/c machos (8 semanas), que foram divididos em dois grupos: sham e séptico. No grupo séptico, a sepse foi induzida por ligadura e perfuração transversal do ceco com agulha 26G. No grupo sham, a etapa de perfuração transversal do ceco não foi realizada. 6 horas após a indução da sepse, o papel do PVAT no tônus vascular foi avaliado em aortas torácicas dos grupos sham e séptico. Nossos resultados demonstram que apesar dos grupos sham e séptico apresentarem 100% de sobrevida, o grupo séptico apresentou leucopenia marcada por neutropenia, hipotermia, hipotensão arterial e alta pontuação de escore clínico quando comparado ao grupo sham. A vasoconstrição induzida por fenilefrina foi significativamente reduzida no grupo séptico em comparação ao grupo sham na ausência de PVAT. Entretanto, na presença do PVAT, o prejuízo na contratilidade vascular observado no grupo séptico foi reestabelecido. Ou seja, o PVAT apresentou um perfil vasoconstritor, se contrapondo a hiporreatividade causada pela sepse. Entre os mecanismos envolvidos nesse processo, sugerimos uma regulação recíproca entre espécies reativas de oxigênio, neste caso, ânion superóxido, gerado provavelmente a partir do complexo NADPH oxidase, e que por uma cascata de autoperpetuação, a COX-2 e seus derivados vasocontráteis, como tromboxano A2 e prostaglandina F2α também atuam “alimentando” essa via. Portanto sugerimos que o perfil contrátil apresentado pelo PVAT na sepse aguda (6h) se deva principalmente à participação de ânions superóxido, além de derivados da COX-2 e que ambos “autoalimentam” o ciclo favorecendo a contração observada.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas GeraisCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorUniversidade Federal de Minas GeraisBrasilICB - DEPARTAMENTO DE FARMACOLOGIAPrograma de Pós-Graduação em Ciências Biológicas - Fisiologia e FarmacologiaUFMGDaniella Bonaventurahttp://lattes.cnpq.br/9290907947235226Steyner de França CôrtesLuciano dos Santos Aggum CapettiniNaiara de Assis Rabelo Ribeiro2021-02-24T17:05:02Z2021-02-24T17:05:02Z2020-12-04info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/1843/35058porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMG2021-02-24T17:05:02Zoai:repositorio.ufmg.br:1843/35058Repositório InstitucionalPUBhttps://repositorio.ufmg.br/oairepositorio@ufmg.bropendoar:2021-02-24T17:05:02Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
dc.title.none.fl_str_mv Caracterização do efeito do tecido adiposo perivascular (PVAT) em aortas de camundongos submetidos a sepse aguda
title Caracterização do efeito do tecido adiposo perivascular (PVAT) em aortas de camundongos submetidos a sepse aguda
spellingShingle Caracterização do efeito do tecido adiposo perivascular (PVAT) em aortas de camundongos submetidos a sepse aguda
Naiara de Assis Rabelo Ribeiro
PVAT
Sepse
Hiporreatividade
COX
Estresse oxidativo
Tecido adiposo
Vasos sanguíneos
Aorta
Sepse
Ciclo-oxigenase 2
Estresse oxidativo
title_short Caracterização do efeito do tecido adiposo perivascular (PVAT) em aortas de camundongos submetidos a sepse aguda
title_full Caracterização do efeito do tecido adiposo perivascular (PVAT) em aortas de camundongos submetidos a sepse aguda
title_fullStr Caracterização do efeito do tecido adiposo perivascular (PVAT) em aortas de camundongos submetidos a sepse aguda
title_full_unstemmed Caracterização do efeito do tecido adiposo perivascular (PVAT) em aortas de camundongos submetidos a sepse aguda
title_sort Caracterização do efeito do tecido adiposo perivascular (PVAT) em aortas de camundongos submetidos a sepse aguda
author Naiara de Assis Rabelo Ribeiro
author_facet Naiara de Assis Rabelo Ribeiro
author_role author
dc.contributor.none.fl_str_mv Daniella Bonaventura
http://lattes.cnpq.br/9290907947235226
Steyner de França Côrtes
Luciano dos Santos Aggum Capettini
dc.contributor.author.fl_str_mv Naiara de Assis Rabelo Ribeiro
dc.subject.por.fl_str_mv PVAT
Sepse
Hiporreatividade
COX
Estresse oxidativo
Tecido adiposo
Vasos sanguíneos
Aorta
Sepse
Ciclo-oxigenase 2
Estresse oxidativo
topic PVAT
Sepse
Hiporreatividade
COX
Estresse oxidativo
Tecido adiposo
Vasos sanguíneos
Aorta
Sepse
Ciclo-oxigenase 2
Estresse oxidativo
description Perivascular adipose tissue (PVAT) lines the adventitial layer and surrounds most blood vessels. PVAT releases biologically active molecules that regulate vascular tone. Knowing the importance of this tissue in the control of vascular tone and that the systemic hypotension, generated in a case of sepsis, is the main cause of death, this study aimed to study the vasoactive and inflammatory effects of PVAT on aortic hyporeactivity induced by acute sepsis. For this purpose, male Balb / c mice (8 weeks) were used, which were divided into two groups: sham and septic. In the septic group, sepsis was induced by ligation and transverse perforation of the cecum with a 26G needle. In the sham group, the transverse perforation step of the cecum was not performed. 6 hours after sepsis induction, the role of PVAT in vascular tone was assessed in thoracic aortas of the sham and septic groups. Our results demonstrate that although the sham and septic groups have 100% survival, the septic group presented leukopenia marked by neutropenia, hypothermia, arterial hypotension, and a high clinical score when compared to the sham group. Phenylephrine-induced vasoconstriction was significantly reduced in the septic group compared to the sham group in the absence of PVAT. However, in the presence of PVAT, the impairment of vascular contractility observed in the septic group was reestablished. In other words, PVAT presented a vasoconstrictor profile, in contrast to the hyporeactivity caused by sepsis. Among the mechanisms involved in this process, we suggest a reciprocal regulation between reactive oxygen species, in this case, superoxide anion, probably generated from the NADPH oxidase complex, and that by a self-perpetuating cascade, COX-2 and its vasocontractable derivatives, as thromboxane A2 and prostaglandin F2α also act "feeding" this pathway. Therefore, we suggest that the contractile profile presented by PVAT in acute sepsis (6h) is mainly due to the participation of superoxide anions, in addition to derivatives of COX-2 and that both “feed” the cycle favoring the observed contraction.
publishDate 2020
dc.date.none.fl_str_mv 2020-12-04
2021-02-24T17:05:02Z
2021-02-24T17:05:02Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1843/35058
url http://hdl.handle.net/1843/35058
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Minas Gerais
Brasil
ICB - DEPARTAMENTO DE FARMACOLOGIA
Programa de Pós-Graduação em Ciências Biológicas - Fisiologia e Farmacologia
UFMG
publisher.none.fl_str_mv Universidade Federal de Minas Gerais
Brasil
ICB - DEPARTAMENTO DE FARMACOLOGIA
Programa de Pós-Graduação em Ciências Biológicas - Fisiologia e Farmacologia
UFMG
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFMG
instname:Universidade Federal de Minas Gerais (UFMG)
instacron:UFMG
instname_str Universidade Federal de Minas Gerais (UFMG)
instacron_str UFMG
institution UFMG
reponame_str Repositório Institucional da UFMG
collection Repositório Institucional da UFMG
repository.name.fl_str_mv Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)
repository.mail.fl_str_mv repositorio@ufmg.br
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