| Autor: |
Guido MC; Vascular Biology Laboratory, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, SP, Brazil.; Laboratory of Metabolism and Lipids, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, SP, Brazil., Debbas V; Vascular Biology Laboratory, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, SP, Brazil., Salemi VM; Heart Failure Unit, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, SP, Brazil., Tavares ER; Laboratory of Metabolism and Lipids, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, SP, Brazil., Meirelles T; Vascular Biology Laboratory, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, SP, Brazil., Araujo TLS; Vascular Biology Laboratory, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, SP, Brazil., Nolasco P; Vascular Biology Laboratory, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, SP, Brazil., Ferreira-Filho JCA; Heart Failure Unit, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, SP, Brazil., Takimura CK; Department of Interventional Cardiology, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, SP, Brazil., Pereira LV; National Laboratory for Embryonic Stem Cells (LaNCE), Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, SP, Brazil., Laurindo FR; Vascular Biology Laboratory, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, SP, Brazil. |
| Abstrakt: |
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 mgΔ 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. |
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