Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/42502
Title: The protein Deleted in Breast Cancer-1 (DBC1) regulates vascular response and formation of aortic dissection during Angiotensin II infusion
Authors: Colman, Laura
Caggiani, Maria
Leyva, Alejandro
Bresque, Mariana
Liechocki, Sally
Maya-Monteiro, Clarissa M.
Mazal, Daniel
Batthyany, Carlos
Calliari, Aldo
Contreras, Paola
Escande, Carlos
Affilliation: 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.
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.
Abstract: 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.
Keywords: Breast Cancer
Angiotensin II infusion
DBC1
Aortic dissection
Vascular response
keywords: Câncer de mama
Proteína
Vascularização
Angiotensina II
Infusão
DBC1
Issue Date: 2020
Publisher: Nature Resaerch
Citation: 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.
DOI: 10.1038/s41598-020-63841-8
ISSN: 2045-2322
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos

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