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 toward DMD disease. Medications that target DMD cardiac fibrosis are in the early stages of development. We found immunoproteasome dysregulation in affected hearts of mdx mice (murine animal model of DMD) and cardiomyocytes derived from induced pluripotent stem cells of patients with DMD. 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 of modulating the immunoproteasome as new and clinically relevant treatment to rescue dilated cardiomyopathy in patients with DMD.
| Original language | English |
|---|---|
| Journal | American Journal of Pathology |
| DOIs | |
| Publication status | E-pub ahead of print - Nov 16 2018 |
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Fibrosis Rescue Improves Cardiac Function in Dystrophin-Deficient Mice and Duchenne Patient-Specific Cardiomyocytes by Immunoproteasome Modulation. / Farini, Andrea; Gowran, Aoife; Bella, Pamela; Sitzia, Clementina; Scopece, Alessandro; Castiglioni, Elisa; Rovina, Davide; Nigro, Patrizia; Villa, Chiara; Fortunato, Francesco; Comi, Giacomo Pietro; Milano, Giuseppina; Pompilio, Giulio; Torrente, Yvan.
In: American Journal of Pathology, 16.11.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Fibrosis Rescue Improves Cardiac Function in Dystrophin-Deficient Mice and Duchenne Patient-Specific Cardiomyocytes by Immunoproteasome Modulation
AU - Farini, Andrea
AU - Gowran, Aoife
AU - Bella, Pamela
AU - Sitzia, Clementina
AU - Scopece, Alessandro
AU - Castiglioni, Elisa
AU - Rovina, Davide
AU - Nigro, Patrizia
AU - Villa, Chiara
AU - Fortunato, Francesco
AU - Comi, Giacomo Pietro
AU - Milano, Giuseppina
AU - Pompilio, Giulio
AU - Torrente, Yvan
N1 - Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
PY - 2018/11/16
Y1 - 2018/11/16
N2 - 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 toward DMD disease. Medications that target DMD cardiac fibrosis are in the early stages of development. We found immunoproteasome dysregulation in affected hearts of mdx mice (murine animal model of DMD) and cardiomyocytes derived from induced pluripotent stem cells of patients with DMD. 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 of modulating the immunoproteasome as new and clinically relevant treatment to rescue dilated cardiomyopathy in patients with DMD.
AB - 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 toward DMD disease. Medications that target DMD cardiac fibrosis are in the early stages of development. We found immunoproteasome dysregulation in affected hearts of mdx mice (murine animal model of DMD) and cardiomyocytes derived from induced pluripotent stem cells of patients with DMD. 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 of modulating the immunoproteasome as new and clinically relevant treatment to rescue dilated cardiomyopathy in patients with DMD.
U2 - 10.1016/j.ajpath.2018.10.010
DO - 10.1016/j.ajpath.2018.10.010
M3 - Article
C2 - 30448404
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
ER -