In situ Evidence of Collagen V and Interleukin-6/Interleukin-17 Activation in Vascular Remodeling of Experimental Pulmonary Hypertension
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1159/000510048 http://hdl.handle.net/11449/210416 |
Resumo: | Several studies have reported the pathophysiologic and molecular mechanisms responsible for pulmonary arterial hypertension (PAH). However, the in situ evidence of collagen V (Col V) and interleukin-17 (IL-17)/interleukin-6 (IL-6) activation in PAH has not been fully elucidated. We analyzed the effects of collagen I (Col I), Col V, IL-6, and IL-17 on vascular remodeling and hemodynamics and its possible mechanisms of action in monocrotaline (MCT)-induced PAH. Twenty male Wistar rats were randomly divided into two groups. In the PAH group, animals received MCT 60 mg/kg intraperitoneally, whereas the control group (CTRL) received saline. On day 21, the pulmonary blood pressure (PAP) and right ventricular systolic pressure (RVSP) were determined. Lung histology (smooth muscle cell proliferation [alpha-smooth muscle actin; alpha-SMA] and periadventitial fibrosis), immunofluorescence (Col I, Col V, and alpha-SMA), immunohistochemistry (IL-6, IL-17, and transforming growth factor-beta [TGF-beta]), and transmission electron microscopy to detect fibronexus were evaluated. The RVSP (40 +/- 2 vs. 24 +/- 1 mm Hg, respectively; p < 0.0001), right ventricle hypertrophy index (65 +/- 9 and 25 +/- 5%, respectively; p < 0.0001), vascular periadventitial Col I and Col V, smooth muscle cell alpha-SMA+, fibronexus, IL-6, IL-17, and TGF-beta were higher in the MCT group than in the CTRL group. In conclusion, our findings indicate in situ evidence of Col V and IL-6/IL-17 activation in vascular remodeling and suggest that increase of Col V may yield potential therapeutic targets for treating patients with PAH. |
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In situ Evidence of Collagen V and Interleukin-6/Interleukin-17 Activation in Vascular Remodeling of Experimental Pulmonary HypertensionCollagen type VCollagen type IMonocrotalinePulmonary arterial hypertensionImmunofluorescenceInterleukin-6Interleukin-17Several studies have reported the pathophysiologic and molecular mechanisms responsible for pulmonary arterial hypertension (PAH). However, the in situ evidence of collagen V (Col V) and interleukin-17 (IL-17)/interleukin-6 (IL-6) activation in PAH has not been fully elucidated. We analyzed the effects of collagen I (Col I), Col V, IL-6, and IL-17 on vascular remodeling and hemodynamics and its possible mechanisms of action in monocrotaline (MCT)-induced PAH. Twenty male Wistar rats were randomly divided into two groups. In the PAH group, animals received MCT 60 mg/kg intraperitoneally, whereas the control group (CTRL) received saline. On day 21, the pulmonary blood pressure (PAP) and right ventricular systolic pressure (RVSP) were determined. Lung histology (smooth muscle cell proliferation [alpha-smooth muscle actin; alpha-SMA] and periadventitial fibrosis), immunofluorescence (Col I, Col V, and alpha-SMA), immunohistochemistry (IL-6, IL-17, and transforming growth factor-beta [TGF-beta]), and transmission electron microscopy to detect fibronexus were evaluated. The RVSP (40 +/- 2 vs. 24 +/- 1 mm Hg, respectively; p < 0.0001), right ventricle hypertrophy index (65 +/- 9 and 25 +/- 5%, respectively; p < 0.0001), vascular periadventitial Col I and Col V, smooth muscle cell alpha-SMA+, fibronexus, IL-6, IL-17, and TGF-beta were higher in the MCT group than in the CTRL group. In conclusion, our findings indicate in situ evidence of Col V and IL-6/IL-17 activation in vascular remodeling and suggest that increase of Col V may yield potential therapeutic targets for treating patients with PAH.Univ Sao Paulo, Riberao Preto Med Sch, Dept Pathol & Legal Med, Ribeirao Preto, BrazilSao Paulo State Univ, Botucatu Med Sch, Botucatu, SP, BrazilUniv Sao Paulo, Fac Med, Rheumatol Div Hosp Clin, Sao Paulo, BrazilUniv Fed Rio de Janeiro, Ctr Ciencias Saude, Carlos Chagas Filho Biophys Inst, Lab Pulm Invest, Rio De Janeiro, BrazilNatl Inst Sci & Technol Regenerat Med, Rio De Janeiro, BrazilUniv Sao Paulo, Fac Med, Lab Histomorphometry & Lung Genom, Sao Paulo, BrazilSao Paulo State Univ, Botucatu Med Sch, Botucatu, SP, BrazilKargerUniversidade de São Paulo (USP)Universidade Estadual Paulista (Unesp)Universidade Federal do Rio de Janeiro (UFRJ)Natl Inst Sci & Technol Regenerat MedBatah, Sabrina SetembreAlda, Maiara AlmeidaLopes Roslindo Figueira, Rebeca RodriguesCruvinel, Heloisa R. [UNESP]Rodrigues da Silva, Luis Perdona [UNESP]Machado-Rugolo, Juliana [UNESP]Velosa, Ana PaulaTeodoro, Walcy RosoliaBalancin, MarceloSilva, Pedro LemeCapelozzi, Vera LuizaFabro, Alexandre Todorovic2021-06-25T15:07:57Z2021-06-25T15:07:57Z2020-12-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article356-366http://dx.doi.org/10.1159/000510048Pathobiology. Basel: Karger, v. 87, n. 6, p. 356-366, 2020.1015-2008http://hdl.handle.net/11449/21041610.1159/000510048WOS:000599717500004Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengPathobiologyinfo:eu-repo/semantics/openAccess2021-10-23T20:17:28Zoai:repositorio.unesp.br:11449/210416Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T22:08:01.730485Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
In situ Evidence of Collagen V and Interleukin-6/Interleukin-17 Activation in Vascular Remodeling of Experimental Pulmonary Hypertension |
title |
In situ Evidence of Collagen V and Interleukin-6/Interleukin-17 Activation in Vascular Remodeling of Experimental Pulmonary Hypertension |
spellingShingle |
In situ Evidence of Collagen V and Interleukin-6/Interleukin-17 Activation in Vascular Remodeling of Experimental Pulmonary Hypertension Batah, Sabrina Setembre Collagen type V Collagen type I Monocrotaline Pulmonary arterial hypertension Immunofluorescence Interleukin-6 Interleukin-17 |
title_short |
In situ Evidence of Collagen V and Interleukin-6/Interleukin-17 Activation in Vascular Remodeling of Experimental Pulmonary Hypertension |
title_full |
In situ Evidence of Collagen V and Interleukin-6/Interleukin-17 Activation in Vascular Remodeling of Experimental Pulmonary Hypertension |
title_fullStr |
In situ Evidence of Collagen V and Interleukin-6/Interleukin-17 Activation in Vascular Remodeling of Experimental Pulmonary Hypertension |
title_full_unstemmed |
In situ Evidence of Collagen V and Interleukin-6/Interleukin-17 Activation in Vascular Remodeling of Experimental Pulmonary Hypertension |
title_sort |
In situ Evidence of Collagen V and Interleukin-6/Interleukin-17 Activation in Vascular Remodeling of Experimental Pulmonary Hypertension |
author |
Batah, Sabrina Setembre |
author_facet |
Batah, Sabrina Setembre Alda, Maiara Almeida Lopes Roslindo Figueira, Rebeca Rodrigues Cruvinel, Heloisa R. [UNESP] Rodrigues da Silva, Luis Perdona [UNESP] Machado-Rugolo, Juliana [UNESP] Velosa, Ana Paula Teodoro, Walcy Rosolia Balancin, Marcelo Silva, Pedro Leme Capelozzi, Vera Luiza Fabro, Alexandre Todorovic |
author_role |
author |
author2 |
Alda, Maiara Almeida Lopes Roslindo Figueira, Rebeca Rodrigues Cruvinel, Heloisa R. [UNESP] Rodrigues da Silva, Luis Perdona [UNESP] Machado-Rugolo, Juliana [UNESP] Velosa, Ana Paula Teodoro, Walcy Rosolia Balancin, Marcelo Silva, Pedro Leme Capelozzi, Vera Luiza Fabro, Alexandre Todorovic |
author2_role |
author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade de São Paulo (USP) Universidade Estadual Paulista (Unesp) Universidade Federal do Rio de Janeiro (UFRJ) Natl Inst Sci & Technol Regenerat Med |
dc.contributor.author.fl_str_mv |
Batah, Sabrina Setembre Alda, Maiara Almeida Lopes Roslindo Figueira, Rebeca Rodrigues Cruvinel, Heloisa R. [UNESP] Rodrigues da Silva, Luis Perdona [UNESP] Machado-Rugolo, Juliana [UNESP] Velosa, Ana Paula Teodoro, Walcy Rosolia Balancin, Marcelo Silva, Pedro Leme Capelozzi, Vera Luiza Fabro, Alexandre Todorovic |
dc.subject.por.fl_str_mv |
Collagen type V Collagen type I Monocrotaline Pulmonary arterial hypertension Immunofluorescence Interleukin-6 Interleukin-17 |
topic |
Collagen type V Collagen type I Monocrotaline Pulmonary arterial hypertension Immunofluorescence Interleukin-6 Interleukin-17 |
description |
Several studies have reported the pathophysiologic and molecular mechanisms responsible for pulmonary arterial hypertension (PAH). However, the in situ evidence of collagen V (Col V) and interleukin-17 (IL-17)/interleukin-6 (IL-6) activation in PAH has not been fully elucidated. We analyzed the effects of collagen I (Col I), Col V, IL-6, and IL-17 on vascular remodeling and hemodynamics and its possible mechanisms of action in monocrotaline (MCT)-induced PAH. Twenty male Wistar rats were randomly divided into two groups. In the PAH group, animals received MCT 60 mg/kg intraperitoneally, whereas the control group (CTRL) received saline. On day 21, the pulmonary blood pressure (PAP) and right ventricular systolic pressure (RVSP) were determined. Lung histology (smooth muscle cell proliferation [alpha-smooth muscle actin; alpha-SMA] and periadventitial fibrosis), immunofluorescence (Col I, Col V, and alpha-SMA), immunohistochemistry (IL-6, IL-17, and transforming growth factor-beta [TGF-beta]), and transmission electron microscopy to detect fibronexus were evaluated. The RVSP (40 +/- 2 vs. 24 +/- 1 mm Hg, respectively; p < 0.0001), right ventricle hypertrophy index (65 +/- 9 and 25 +/- 5%, respectively; p < 0.0001), vascular periadventitial Col I and Col V, smooth muscle cell alpha-SMA+, fibronexus, IL-6, IL-17, and TGF-beta were higher in the MCT group than in the CTRL group. In conclusion, our findings indicate in situ evidence of Col V and IL-6/IL-17 activation in vascular remodeling and suggest that increase of Col V may yield potential therapeutic targets for treating patients with PAH. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-12-01 2021-06-25T15:07:57Z 2021-06-25T15:07:57Z |
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.uri.fl_str_mv |
http://dx.doi.org/10.1159/000510048 Pathobiology. Basel: Karger, v. 87, n. 6, p. 356-366, 2020. 1015-2008 http://hdl.handle.net/11449/210416 10.1159/000510048 WOS:000599717500004 |
url |
http://dx.doi.org/10.1159/000510048 http://hdl.handle.net/11449/210416 |
identifier_str_mv |
Pathobiology. Basel: Karger, v. 87, n. 6, p. 356-366, 2020. 1015-2008 10.1159/000510048 WOS:000599717500004 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Pathobiology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
356-366 |
dc.publisher.none.fl_str_mv |
Karger |
publisher.none.fl_str_mv |
Karger |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808129395336937472 |