학술논문
Ryanodine receptor dysfunction causes senescence and fibrosis in Duchenne dilated cardiomyopathy
Document Type
article
Author
Monia Souidi; Jessica Resta; Haikel Dridi; Yvonne Sleiman; Steve Reiken; Karina Formoso; Sarah Colombani; Pascal Amédro; Pierre Meyer; Azzouz Charrabi; Marie Vincenti; Yang Liu; Rajesh Kumar Soni; Frank Lezoualc'h; D.V.M. Stéphane Blot; François Rivier; Olivier Cazorla; Angelo Parini; Andrew R. Marks; Jeanne Mialet‐Perez; Alain Lacampagne; Albano C. Meli
Source
Journal of Cachexia, Sarcopenia and Muscle, Vol 15, Iss 2, Pp 536-551 (2024)
Subject
Language
English
ISSN
2190-6009
2190-5991
2190-5991
Abstract
Abstract Background Duchenne muscular dystrophy (DMD) is an X‐linked disorder characterized by progressive muscle weakness due to the absence of functional dystrophin. DMD patients also develop dilated cardiomyopathy (DCM). We have previously shown that DMD (mdx) mice and a canine DMD model (GRMD) exhibit abnormal intracellular calcium (Ca2+) cycling related to early‐stage pathological remodelling of the ryanodine receptor intracellular calcium release channel (RyR2) on the sarcoplasmic reticulum (SR) contributing to age‐dependent DCM. Methods Here, we used hiPSC‐CMs from DMD patients selected by Speckle‐tracking echocardiography and canine DMD cardiac biopsies to assess key early‐stage Duchenne DCM features. Results Dystrophin deficiency was associated with RyR2 remodelling and SR Ca2+ leak (RyR2 Po of 0.03 ± 0.01 for HC vs. 0.16 ± 0.01 for DMD, P