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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Peri/Epicellular Protein Disulfide Isomerase Sustains Vascular Lumen Caliber Through an Anticonstrictive Remodeling Effect

Texto completo
Autor(es):
Tanaka, Leonardo Y. [1] ; Araujo, Haniel A. [1] ; Hironaka, Gustavo K. [1] ; Araujo, Thais L. S. [1] ; Takimura, Celso K. [2] ; Rodriguez, Andres I. [1] ; Casagrande, Annelise S. [1] ; Gutierrez, Paulo S. [3] ; Lemos-Neto, Pedro Alves [2] ; Laurindo, Francisco R. M. [1]
Número total de Autores: 10
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Sch Med, Vasc Biol Lab, Heart Inst InCor, Ave Eneas C Aguiar, 44, Annex 2, 9th Floor, BR-05403000 Sao Paulo - Brazil
[2] Univ Sao Paulo, Sch Med, Intervent Cardiol Unit, Heart Inst InCor, BR-05403000 Sao Paulo - Brazil
[3] Univ Sao Paulo, Sch Med, Pathol Lab, Heart Inst InCor, BR-05403000 Sao Paulo - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: Hypertension; v. 67, n. 3, p. 613-622, MAR 2016.
Citações Web of Science: 13
Resumo

Whole-vessel remodeling critically determines lumen caliber in vascular (patho)physiology, and it is reportedly redox-dependent. We hypothesized that the cell-surface pool of the endoplasmic reticulum redox chaperone protein disulfide isomerase-A1 (peri/epicellular=pecPDI), which is known to support thrombosis, also regulates disease-associated vascular architecture. In human coronary atheromas, PDI expression inversely correlated with constrictive remodeling and plaque stability. In a rabbit iliac artery overdistension model, there was unusually high PDI upregulation (approximate to 25-fold versus basal, 14 days postinjury), involving both intracellular and pecPDI. PecPDI neutralization with distinct anti-PDI antibodies did not enhance endoplasmic reticulum stress or apoptosis. In vivo pecPDI neutralization with PDI antibody-containing perivascular gel from days 12 to 14 post injury promoted 25% decrease in the maximally dilated arteriographic vascular caliber. There was corresponding whole-vessel circumference loss using optical coherence tomography without change in neointima, which indicates constrictive remodeling. This was accompanied by decreased hydrogen peroxide generation. Constrictive remodeling was corroborated by marked changes in collagen organization, that is, switching from circumferential to radial fiber orientation and to a more rigid fiber type. The cytoskeleton architecture was also disrupted; there was a loss of stress fiber coherent organization and a switch from thin to medium thickness actin fibers, all leading to impaired viscoelastic ductility. Total and PDI-associated expressions of 1-integrin, and levels of reduced cell-surface 1-integrin, were diminished after PDI antibody treatment, implicating 1-integrin as a likely pecPDI target during vessel repair. Indeed, focal adhesion kinase phosphorylation, a downstream 1-integrin effector, was decreased by PDI antibody. Thus, the upregulated pecPDI pool tunes matrix/cytoskeleton reshaping to counteract inward remodeling in vascular pathophysiology. (AU)

Processo FAPESP: 13/06241-0 - Modelo de interação entre dissulfeto-isomerase proteica e RhoGTPases e seu regulador RhoGDI durante a ativação do complexo NADPH oxidase em células musculares lisas
Beneficiário:Andrés Ignacio Rodríguez Morales
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 13/07937-8 - Redoxoma
Beneficiário:Ohara Augusto
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 09/51654-5 - Dissulfeto isomerase proteica como via integrativa entre estresse oxidativo e resposta a proteínas mal-enoveladas na reparação a lesão vascular
Beneficiário:Leonardo Yuji Tanaka
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 10/06360-0 - Estudo de expressão gênica na resposta de reparação vascular à lesão: efeitos da supressão da dissulfeto isomerase protéica
Beneficiário:Haniel Alves Araujo
Linha de fomento: Bolsas no Brasil - Iniciação Científica
Processo FAPESP: 09/54764-6 - Regulação da homeostase redox e resposta integrada a estresse pela dissulfeto isomerase protéica (PDI): mecanismos e papel na fisiopatologia e terapêutica de doenças vasculares
Beneficiário:Francisco Rafael Martins Laurindo
Linha de fomento: Auxílio à Pesquisa - Temático