The protein Deleted in Breast Cancer-1 (DBC1) regulates vascular response and formation of aortic dissection during Angiotensin II infusion

Detalhes bibliográficos
Autor(a) principal: Colman, Laura
Data de Publicação: 2020
Outros Autores: Caggiani, Maria, Leyva, Alejandro, Bresque, Mariana, Liechocki, Sally, Maya-Monteiro, Clarissa M., Mazal, Daniel, Batthyany, Carlos, Calliari, Aldo, Contreras, Paola, Escande, Carlos
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/42502
Resumo: Institut Pasteur Montevideo. Laboratory of Metabolic Diseases and Aging, INDICyO Program. Montevideo, Uruguay.
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spelling Colman, LauraCaggiani, MariaLeyva, AlejandroBresque, MarianaLiechocki, SallyMaya-Monteiro, Clarissa M.Mazal, DanielBatthyany, CarlosCalliari, AldoContreras, PaolaEscande, Carlos2020-08-01T20:24:01Z2020-08-01T20:24:01Z2020COLMAN, Laura et al. The protein Deleted in Breast Cancer-1 (DBC1) regulates vascular response and formation of aortic dissection during Angiotensin II infusion. Scientific Reports, v. 10, n. 6772, p. 1-22, 2020.2045-2322https://www.arca.fiocruz.br/handle/icict/4250210.1038/s41598-020-63841-8engNature ResaerchCâncer de mamaProteínaVascularizaçãoAngiotensina IIInfusãoDBC1Breast CancerAngiotensin II infusionDBC1Aortic dissectionVascular responseThe protein Deleted in Breast Cancer-1 (DBC1) regulates vascular response and formation of aortic dissection during Angiotensin II infusioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleInstitut Pasteur Montevideo. Laboratory of Metabolic Diseases and Aging, INDICyO Program. Montevideo, Uruguay.Institut Pasteur Montevideo. Laboratory of Metabolic Diseases and Aging, INDICyO Program. Montevideo, Uruguay.Institut Pasteur Montevideo. Laboratory of Metabolic Diseases and Aging, INDICyO Program. Montevideo, Uruguay / Universidad de la República (UdelaR). Facultad de Medicina. Departamento de Fisiologia. Montevideo, Uruguay.Institut Pasteur Montevideo. INDICyO Program. Laboratory of Vascular Biology and Rational Drug Design. Montevideo, Uruguay / Institut Pasteur Montevideo and Instituto de Investigaciones Biológicas Clemente Estable. Analytical Biochemistry and Proteomics Unit. Montevideo, Uruguay.Institut Pasteur Montevideo. Laboratory of Metabolic Diseases and Aging, INDICyO Program. Montevideo, Uruguay.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidad de la República (UdelaR) and C.H Pereira Rossell. Facultad de Medicina. Departamento de Anatomía Patológica. Montevideo, Uruguay.Institut Pasteur Montevideo. Laboratory of Vascular Biology and Rational Drug Design, INDICyO Program. Montevideo, Uruguay.Institut Pasteur Montevideo. Laboratory of Metabolic Diseases and Aging, INDICyO Program. Montevideo, Uruguay / Universidad de la República (UdelaR). Facultad de Veterinaria. Departamento de Biociencias. Montevideo, Uruguay.Institut Pasteur Montevideo. Laboratory of Metabolic Diseases and Aging, INDICyO Program. Montevideo, Uruguay / Universidad de la República (UdelaR). Facultad de Medicina. Departamento de Fisiología. Montevideo, Uruguay.Institut Pasteur Montevideo. Laboratory of Metabolic Diseases and Aging, INDICyO Program. Montevideo, Uruguay / Universidad de la República (UdelaR). Facultad de Medicina. Departamento de Anatomía Patológica. Montevideo, Uruguay.Cardiovascular diseases are among the main causes of morbimortality in the adult population. Among them, hypertension is a leading cause for stroke, heart disease and kidney failure. Also, as a result of arterial wall weakness, hypertension can lead to the development of dissecting aortic aneurysms, a rare but often fatal condition if not readily treated. In this work, we investigated the role of DBC1 in the regulation of vascular function in an ANGII-induced hypertension mouse model. We found that WT and DBC1 KO mice developed hypertension in response to ANGII infusion. However, DBC1 KO mice showed increased susceptibility to develop aortic dissections. The effect was accompanied by upregulation of vascular remodeling factors, including MMP9 and also VEGF. Consistent with this, we found decreased collagen deposition and elastic fiber fragmentation, suggesting that increased expression of MMPs in DBC1 KO mice weakens the arterial wall, promoting the formation of aortic dissections during treatment with ANGII. Finally, DBC1 KO mice had reduced cell proliferation in the intima-media layer in response to ANGII, paralleled with an impairment to increase wall thickness in response to hypertension. Furthermore, VSMC purified from DBC1 KO mice showed impaired capacity to leave quiescence, confirming the in vivo results. Altogether, our results show for the first time that DBC1 regulates vascular response and function during hypertension and protects against vascular injury. This work also brings novel insights into the molecular mechanisms of the development of aortic dissections.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/42502/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALSallyLiechocki)ClarissaMMonteiro_etal_IOC_2020.pdfSallyLiechocki)ClarissaMMonteiro_etal_IOC_2020.pdfapplication/pdf7595214https://www.arca.fiocruz.br/bitstream/icict/42502/2/SallyLiechocki%29ClarissaMMonteiro_etal_IOC_2020.pdfbe2ba2832375a4f17942fafa652a63dcMD52TEXTSallyLiechocki)ClarissaMMonteiro_etal_IOC_2020.pdf.txtSallyLiechocki)ClarissaMMonteiro_etal_IOC_2020.pdf.txtExtracted texttext/plain67550https://www.arca.fiocruz.br/bitstream/icict/42502/3/SallyLiechocki%29ClarissaMMonteiro_etal_IOC_2020.pdf.txtb87e530b67c404c476a24c845bc5949eMD53icict/425022020-08-03 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dc.title.pt_BR.fl_str_mv The protein Deleted in Breast Cancer-1 (DBC1) regulates vascular response and formation of aortic dissection during Angiotensin II infusion
title The protein Deleted in Breast Cancer-1 (DBC1) regulates vascular response and formation of aortic dissection during Angiotensin II infusion
spellingShingle The protein Deleted in Breast Cancer-1 (DBC1) regulates vascular response and formation of aortic dissection during Angiotensin II infusion
Colman, Laura
Câncer de mama
Proteína
Vascularização
Angiotensina II
Infusão
DBC1
Breast Cancer
Angiotensin II infusion
DBC1
Aortic dissection
Vascular response
title_short The protein Deleted in Breast Cancer-1 (DBC1) regulates vascular response and formation of aortic dissection during Angiotensin II infusion
title_full The protein Deleted in Breast Cancer-1 (DBC1) regulates vascular response and formation of aortic dissection during Angiotensin II infusion
title_fullStr The protein Deleted in Breast Cancer-1 (DBC1) regulates vascular response and formation of aortic dissection during Angiotensin II infusion
title_full_unstemmed The protein Deleted in Breast Cancer-1 (DBC1) regulates vascular response and formation of aortic dissection during Angiotensin II infusion
title_sort The protein Deleted in Breast Cancer-1 (DBC1) regulates vascular response and formation of aortic dissection during Angiotensin II infusion
author Colman, Laura
author_facet Colman, Laura
Caggiani, Maria
Leyva, Alejandro
Bresque, Mariana
Liechocki, Sally
Maya-Monteiro, Clarissa M.
Mazal, Daniel
Batthyany, Carlos
Calliari, Aldo
Contreras, Paola
Escande, Carlos
author_role author
author2 Caggiani, Maria
Leyva, Alejandro
Bresque, Mariana
Liechocki, Sally
Maya-Monteiro, Clarissa M.
Mazal, Daniel
Batthyany, Carlos
Calliari, Aldo
Contreras, Paola
Escande, Carlos
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Colman, Laura
Caggiani, Maria
Leyva, Alejandro
Bresque, Mariana
Liechocki, Sally
Maya-Monteiro, Clarissa M.
Mazal, Daniel
Batthyany, Carlos
Calliari, Aldo
Contreras, Paola
Escande, Carlos
dc.subject.other.pt_BR.fl_str_mv Câncer de mama
Proteína
Vascularização
Angiotensina II
Infusão
DBC1
topic Câncer de mama
Proteína
Vascularização
Angiotensina II
Infusão
DBC1
Breast Cancer
Angiotensin II infusion
DBC1
Aortic dissection
Vascular response
dc.subject.en.pt_BR.fl_str_mv Breast Cancer
Angiotensin II infusion
DBC1
Aortic dissection
Vascular response
description Institut Pasteur Montevideo. Laboratory of Metabolic Diseases and Aging, INDICyO Program. Montevideo, Uruguay.
publishDate 2020
dc.date.accessioned.fl_str_mv 2020-08-01T20:24:01Z
dc.date.available.fl_str_mv 2020-08-01T20:24:01Z
dc.date.issued.fl_str_mv 2020
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.citation.fl_str_mv COLMAN, Laura et al. The protein Deleted in Breast Cancer-1 (DBC1) regulates vascular response and formation of aortic dissection during Angiotensin II infusion. Scientific Reports, v. 10, n. 6772, p. 1-22, 2020.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/42502
dc.identifier.issn.pt_BR.fl_str_mv 2045-2322
dc.identifier.doi.none.fl_str_mv 10.1038/s41598-020-63841-8
identifier_str_mv COLMAN, Laura et al. The protein Deleted in Breast Cancer-1 (DBC1) regulates vascular response and formation of aortic dissection during Angiotensin II infusion. Scientific Reports, v. 10, n. 6772, p. 1-22, 2020.
2045-2322
10.1038/s41598-020-63841-8
url https://www.arca.fiocruz.br/handle/icict/42502
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Nature Resaerch
publisher.none.fl_str_mv Nature Resaerch
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
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