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Biomarkers of cardiomyopathy in muscle dystrophy : metabolomics and therapy with omega-3

Author(s):
Adriana Fogagnolo Mauricio
Total Authors: 1
Document type: Doctoral Thesis
Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
Defense date:
Examining board members:
Ana Carolina de Mattos Zeri; Luis Garcia Alonso; Rosana Macher Teodori; Lucia Elvira Alvares
Advisor: Maria Julia Marques
Abstract

In Duchenne muscular dystrophy (DMD) and in the mdx mice model of DMD, the absence of dystrophin leads to progressive muscular weakness and cardiorespiratory failure. Corticoids are the choice therapy for DMD. However, due to their side effects other drugs are investigated. Previously, we demonstrated that omega-3 attenuated myonecrosis in skeletal muscles of the mdx mice, during an early stage of the disease (one month old). In the present study, we evaluated whether omega-3 would benefit the dystrophic heart, at later stages of the disease (13 and 17 months). We used morphological (morphometry), molecular (Western bloting) and functional (electrocardiogram) analysis and performed the metabolic profile of mdx heart and diaphragm muscles. In heart, omega-3 decreased cardiac creatine kinase and the levels of TNF-??and MMP-9 (pro-inflammatory markers), TRPC1 (calcium channel) and HNE-4 (marker of oxidative stress); omega-3 reduced heart total content of calcium, and improved some ECG parameters; the effects on cardiac fibrosis were best seen at the later stage of the disease (17 months). In diaphragm, omega-3 improved dystrophinopathy by reducing fibrosis and molecular markers of the disease (TNF-?, TGF-?1, MMP-9 and 4-HNE). The analysis of metabolome showed that metabolites related to energy metabolism (valine) and oxidative stress (oxypurinol and aspartate) were altered in mdx heart and diaphragm, suggesting their use as potential biomarkers at later stages of the disease. Omega-3 affected the metabolic profile of both muscles. While care must be taken to translate data from mice to human diseases, the present results support the use of omega-3 as an additional therapy or nutritional support to DMD patients, deserving future clinical studies. (AU)

FAPESP's process: 12/13577-1 - Biomarkers of cardiomyopathy in dystrophy: a metabolomic study and pharmacological therapy
Grantee:Adriana Fogagnolo Mauricio
Support type: Scholarships in Brazil - Doctorate