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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.)

Effect of the Antioxidant Lipoic Acid in Aortic Phenotype in a Marfan Syndrome Mouse Model

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Autor(es):
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Guido, Maria C. [1, 2] ; Debbas, Victor [1] ; Salemi, Vera M. [3] ; Tavares, Elaine R. [2] ; Meirelles, Thayna [1] ; Araujo, Thais L. S. [1] ; Nolasco, Patricia [1] ; Ferreira-Filho, Julio C. A. [3] ; Takimura, Celso K. [4] ; Pereira, Lygia V. [5] ; Laurindo, Francisco R. [1]
Número total de Autores: 11
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Sch Med, Heart Inst InCor, Vasc Biol Lab, Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Sch Med, Heart Inst InCor, Lab Metab & Lipids, Sao Paulo, SP - Brazil
[3] Univ Sao Paulo, Sch Med, Heart Inst InCor, Heart Failure Unit, Sao Paulo, SP - Brazil
[4] Univ Sao Paulo, Sch Med, Heart Inst InCor, Dept Intervent Cardiol, Sao Paulo, SP - Brazil
[5] Univ Sao Paulo, Inst Biosci, Dept Genet & Evolutionary Biol, Natl Lab Embryon Stem Cells LaNCE, Sao Paulo, SP - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: OXIDATIVE MEDICINE AND CELLULAR LONGEVITY; 2018.
Citações Web of Science: 0
Resumo

Marfan syndrome (MFS) cardiovascular manifestations such as aortic aneurysms and cardiomyopathy carry substantial morbidity/mortality. We investigated the effects of lipoic acid, an antioxidant, on ROS production and aortic remodeling in a MFS mg Delta(loxPneo) mouse model. MFS and WT (wild-type) 1-month-old mice were allocated to 3 groups: untreated, treated with losartan, and treated with lipoic acid. At 6 months old, echocardiography, ROS production, and morphological analysis of aortas were performed. Aortic ROS generation in 6-month-old MFS animals was higher at advanced stages of disease in MFS. An unprecedented finding in MFS mice analyzed by OCT was the occurrence of focal inhomogeneous regions in the aortic arch, either collagen-rich extremely thickened or collagen-poor hypotrophic regions. MFS animals treated with lipoic acid showed markedly reduced ROS production and lower ERK1/2 phosphorylation; meanwhile, aortic dilation and elastic fiber breakdown were unaltered. Of note, lipoic acid treatment associated with the absence of focal inhomogeneous regions in MFS animals. Losartan reduced aortic dilation and elastic fiber breakdown despite no change in ROS generation. In conclusion, oxidant generation by itself seems neutral with respect to aneurysm progression in MFS; however, lipoic acid-mediated reduction of inhomogeneous regions may potentially associate with less anisotropy and reduced chance of dissection/rupture. (AU)

Processo FAPESP: 09/51923-6 - Processos redox na fisiopatologia vascular da Síndrome de Marfan: papel da dissulfeto isomerase proteica e sua associação com fibrilina-1 e NADPH oxidase
Beneficiário:Maria Carolina Guido
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: 09/54764-6 - 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