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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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]
Total Authors: 11
[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
Total Affiliations: 5
Document type: Journal article
Web of Science Citations: 0

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)

FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
Grantee:Ohara Augusto
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 09/54764-6 - Regulation of redox homeostasis and integrated stress response by Protein Disulfide Isomerase (PDI): mechanisms and role in the pathophysiology and therapy of vascular diseases
Grantee:Francisco Rafael Martins Laurindo
Support type: Research Projects - Thematic Grants