Diaphragm degeneration and cardiac structure in mdx mouse: potential clinical implications for Duchenne muscular dystrophy

Autor(es)

Chagas Barbin, Isabel Cristina ^[1] ; Pereira, Juliano Alves ^[1] ; Rovere, Matheus Bersan ^[1] ; Moreira, Drielen de Oliveira ^[1] ; Marques, Maria Julia ^[1] ; Santo Neto, Humberto ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas UNICAMP, Inst Biol, Dept Biol Estrut & Func, BR-13083970 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Anatomy; v. 228, n. 5, p. 784-791, MAY 2016.
• Citações Web of Science: 10

Resumo

We examined the effects of exercise on diaphragm degeneration and cardiomyopathy in dystrophin-deficient mdx mice. Mdx mice (11months of age) were exercised (swimming) for 2months to worsen diaphragm degeneration. Control mdx mice were kept sedentary. Morphological evaluation demonstrated increased fibrosis in the diaphragm of exercised mdx mice (33.3 +/- 6.0% area of fibrosis) compared with control mdx mice (20.9 +/- 1.7% area of fibrosis). Increased (26%) activity of MMP-2, a marker of fibrosis, was detected in the diaphragms from exercised mdx mice. Morphological evaluation of the heart demonstrated a 45% increase in fibrosis in the right ventricle (8.3 +/- 0.6% in sedentary vs. 12.0 +/- 0.6% of fibrosis in exercised) and in the left ventricle (35% increase) in the exercised mdx mice. The density of inflammatory cells-degenerating cardiomyocytes increased 95% in the right ventricle (2.3 +/- 0.6 in sedentary vs. 4.5 +/- 0.8 in exercised) and 71% in the left ventricle (1.4 +/- 0.6 sedentary vs. 2.4 +/- 0.5 exercised). The levels of both active MMP-2 and the pro-fibrotic factor transforming growth factor beta were elevated in the hearts of exercised compared with sedentary mdx mice. The wall thicknesstolumen diameter ratio of the pulmonary trunk was significantly increased in the exercised mdx mice (0.11 +/- 0.04 in sedentary vs. 0.28 +/- 0.12 in exercised), as was the thickness of the right ventricle wall, which suggests the occurrence of pulmonary hypertension in those animals. It is suggested that diaphragm degeneration is a main contributor to right ventricle dystrophic pathology. These findings may be relevant for future interventional studies for Duchenne muscular dystrophy-associated cardiomyopathy. (AU)

• Processo FAPESP: 08/58491-1 - Mecanismos de proteção da distrofia muscular: estudo proteômico e terapia farmacológica
• Beneficiário: Maria Julia Marques
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/04782-6 - Estudos pré-clínicos no camundongo mdx: metabolômica, biomarcadores e terapia com ômega-3
• Beneficiário: Maria Julia Marques
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 04/15526-9 - Proteínas reguladoras do cálcio e proteção à mionecrose na distrofia muscular de Duchenne
• Beneficiário: Maria Julia Marques
• Modalidade de apoio: Auxílio à Pesquisa - Regular