Metabolic shifts and myocyte hypertrophy in deflazacort treatment of mdx mouse cardiomyopathy.

Abstract

We tested the hypothesis that treatment of mdx mouse muscular dystrophy with the glucocorticoid deflazacort prevents cardiomyopathic lesions and is accompanied by changes in metabolism and gene expression that reflect the improved tissue integrity. Cardiac muscle pathology, expression of alpha-cardiac myosin heavy chain, DNA synthesis, laminin, and basic fibroblast growth factor (bFGF) were examined to characterize dystrophy and changes with treatment. The potential of proton magnetic resonance spectroscopy (H-NMRS) to track cardiac dystrophy and deflazacort effects was also studied. Deflazacort (but not equipotent prednisone) reproducibly decreased lesion prevalence and severity. Treatment also produced cardiomyocyte hypertrophy and a 5.4-fold increase in alpha-cardiac myosin content. Expression of bFGF messenger RNA (mRNA), notable around lesions, rose 3.3-fold, and laminin expression rose 2.1-fold after deflazacort. Studies using H-NMRS showed a cardiac "signature" with less glycine and taurine than limb muscle or diaphragm and shifts with progression of dystrophy (distinct from normal aging) in many metabolites. Increased taurine, acetate, and succinate were present after 2 weeks of deflazacort treatment but were not present after 4 weeks. Although paired kinetic and functional studies of myocardium will be needed to determine the origin of such changes, these results demonstrate the potential application of H-NMRS to monitor clinical heart disease and treatment. In addition, the metabolic effects of deflazacort were substantial in preventing the progression of cardiomyopathy in mdx mice and included increased expression of protectant and stabilizing factors and hypertrophy of cardiac myocytes.

• Authors: R Q Skrabek, J E Anderson
• Journal: Muscle & nerve (Muscle Nerve) Vol. 24 Issue 2 Pg. 192-202 (Feb 2001) ISSN: 0148-639X [Print] United States
• PMID: 11180202 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Laminin
• Pregnenediones
• Fibroblast Growth Factor 2
• Taurine
• Myosin Heavy Chains
• deflazacort

Topics

• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Blotting, Northern
• Blotting, Western
• Cardiomyopathies (drug therapy, genetics, metabolism, pathology)
• Fibroblast Growth Factor 2 (biosynthesis)
• Immunohistochemistry
• In Situ Hybridization
• Laminin (biosynthesis)
• Magnetic Resonance Spectroscopy
• Mice
• Mice, Inbred mdx
• Myocardium (chemistry, metabolism)
• Myosin Heavy Chains (metabolism)
• Pregnenediones (therapeutic use)
• Taurine (metabolism)