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

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Guido, Maria C. ; Debbas, Victor ; Salemi, Vera M. ; Tavares, Elaine R. ; Meirelles, Thayna ; Araujo, Thais L. S. ; Nolasco, Patricia ; Ferreira-Filho, Julio C. A. ; Takimura, Celso K. ; Pereira, Lygia V. ; Laurindo, Francisco R.

• Tipo de documento: Artigo Científico
• Fonte: OXIDATIVE MEDICINE AND CELLULAR LONGEVITY; v. 2018, p. 16-pg., 2018-01-01.

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: 13/07937-8 - Redoxoma
• Beneficiário: Ohara Augusto
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• 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
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• 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
• Modalidade de apoio: Auxílio à Pesquisa - Temático