Cardiac and skeletal muscle changes associated with rosuvastatin therapy in dystrophic mdx mice

Autor(es)

Finkler, Julia M. G. ^[1] ; de Carvalho, Samara C. ^[1] ; Neto, Humberto Santo ^[1] ; Marques, Maria J. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Campinas UNICAMP, Inst Biol, Dept Struct & Funct Biol, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Anatomical Record-Advances in Integrative Anatomy and Evolutionary Biology; v. 303, n. 8 DEC 2019.
• Citações Web of Science: 0

Resumo

Statins are prescribed to prevent and treat atherosclerotic cardiovascular and metabolic diseases but have controversial effects on skeletal muscles. While statins are a reported cause of myopathy, some studies have suggested that statins could potentially ameliorate dystrophy due to their pleiotropic effects on inflammation, myonecrosis, and autophagy. In the present study, we evaluated the potential benefit of rosuvastatin treatment on heart, limb, and diaphragm muscles in dystrophin-deficient mdx mice at an early stage (45 days of age) of disease. Mdx mice received rosuvastatin (10 mg/kg) by gavage for 30 days beginning at 15 days of age. Normal C57BL/10 mice received rosuvastatin by the same route over the same interval. In the mdx group, rosuvastatin significantly increased IgG-positive fibers (myonecrosis) and the inflammatory areas in the biceps brachii and diaphragm muscles and decreased the anterior limb muscle force (grip strength). Molecular markers of inflammation (TNF-alpha and NF-kB) and fibrosis (fibronectin) were not altered by rosuvastatin in mdx mice skeletal and cardiac muscles. In normal mice, rosuvastatin increased CK, TNF-alpha (heart), NF-kB (diaphragm), and fibronectin (heart and diaphragm). Inflammatory areas were seen in all normal muscles of rosuvastatin-treated mice. Rosuvastatin did not benefit dystrophy in the mdx mice and was associated with inflammation in normal cardiac and skeletal muscles. (AU)

• Processo FAPESP: 12/15492-3 - Terapia farmacológica das distrofinopatias: fibrose e regeneração muscular em camundongos mdx tratados com ômega-3
• Beneficiário: Samara Camaçarí de Carvalho
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 17/24051-4 - Receptores acoplados a proteína G e autofagia: potenciais alvos do ômega-3 e deflazacorte na terapia farmacológica da DMD
• 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