Patients affected by Duchenne muscular dystrophy (DMD) develop a progressive dilated cardiomyopathy characterized by inflammatory cell infiltration, necrosis, and cardiac fibrosis. Standard treatments consider the use of β‐blockers and angiotensin‐converting enzyme inhibitors that are symptomatic and unspecific towards DMD disease. Medications that target DMD cardiac fibrosis are in early stages of development. Here, we demonstrated immunoproteasome dysregulation in affected hearts of mdx mice (murine animal model of DMD) and cardiomyocytes derived from induced pluripotent stem cells of DMD patients. Interestingly, immunoproteasome inhibition ameliorated cardiomyopathy in mdx mice and reduced the development of cardiac fibrosis. Establishing the immunoproteasome inhibition–dependent cardioprotective role suggests the possibility to modulate the immunoproteasome as novel and clinically relevant treatment to rescue dilated cardiomyopathy in DMD patients.

Fibrosis rescue improves cardiac function in dystrophin-deficient mice and Duchenne patient–specific cardiomyocytes by immunoproteasome modulation / A. Farini, A. Gowran, P. Bella, C. Sitzia, A. Scopece, E. Castiglioni, D. Rovina, P. Nigro, C. Villa, F. Fortunato, G.P. Comi, G. Milano, G. Pompilio, Y. Torrente. - In: THE AMERICAN JOURNAL OF PATHOLOGY. - ISSN 0002-9440. - 189:2(2019 Feb), pp. 339-353. [10.1016/j.ajpath.2018.10.010]

Fibrosis rescue improves cardiac function in dystrophin-deficient mice and Duchenne patient–specific cardiomyocytes by immunoproteasome modulation

C. Villa;G.P. Comi;G. Pompilio
Penultimo
;
Y. Torrente
Ultimo
2019

Abstract

Patients affected by Duchenne muscular dystrophy (DMD) develop a progressive dilated cardiomyopathy characterized by inflammatory cell infiltration, necrosis, and cardiac fibrosis. Standard treatments consider the use of β‐blockers and angiotensin‐converting enzyme inhibitors that are symptomatic and unspecific towards DMD disease. Medications that target DMD cardiac fibrosis are in early stages of development. Here, we demonstrated immunoproteasome dysregulation in affected hearts of mdx mice (murine animal model of DMD) and cardiomyocytes derived from induced pluripotent stem cells of DMD patients. Interestingly, immunoproteasome inhibition ameliorated cardiomyopathy in mdx mice and reduced the development of cardiac fibrosis. Establishing the immunoproteasome inhibition–dependent cardioprotective role suggests the possibility to modulate the immunoproteasome as novel and clinically relevant treatment to rescue dilated cardiomyopathy in DMD patients.
Settore MED/26 - Neurologia
29-nov-2018
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/826311
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