Academic Journal
P2573Modelling the duchenne muscular dystrophy-induced dilated cardiomyopathy using patient-specific induced pluripotent stem cells-derived cardiomyocytes
| العنوان: | P2573Modelling the duchenne muscular dystrophy-induced dilated cardiomyopathy using patient-specific induced pluripotent stem cells-derived cardiomyocytes |
|---|---|
| المؤلفون: | Souidi, M, Sleiman, Y, Moreau, A, Amedro, P, Meyer, P, Rivier, F, Lacampagne, A, Meli, A |
| المصدر: | European Heart Journal ; volume 40, issue Supplement_1 ; ISSN 0195-668X 1522-9645 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Cardiology and Cardiovascular Medicine |
| الوصف: | Introduction Duchenne Muscular Dystrophy (DMD) is a X-linked degenerative pathology with a prevalence of 1/3500 boys due to absence of functional dystrophin in muscles. In a late stage of DMD, patients developed a dilated cardiomyopathy (DCM) which can lead to heart failure and premature death. In the past, we showed that DMD (mdx) mice exhibit a perturbation of the intracellular calcium homeostasis correlated to a pathological remodelling of the calcium ryanodine receptor channel (RyR2) leading to DCM with aging. However, mouse model does not represent a pertinent prototype to study DMD. Human pluripotent stem-cell derived-cardiomyocytes (hiPSC-CMs) are a pertinent tool to model patient-specific inherited cardiac diseases and screen pharmacological drugs in a Petri dish. Objective Based on the clinical history of DMD patients in the local Hospital, our main objective is to model DMD-induced DCM using hiPSC-CMs and compare the functional and molecular features with the clinical echocardiography. To that, we hypothesize that hiPSC-CMs are a powerful technology to model in vitro DCM and to better understand the pathophysiological mechanisms underlying DCM. Methods 3 blood samples from DMD patients with different DCM degrees of severity and 3 from healthy control (HC) were collected, reprogrammed in hiPSC and differentiated into cardiomyocytes. Results Our preliminary data indicate that DMD hiPSC-CMs present an abnormal intracellular calcium homeostasis characterized by the presence of leaky diastolic calcium events compared to HC hiPSC-CMs suggesting a RyR2 dysfunction. In DMD hiPSC-CMs, we also observe alterations in the contractile properties and a perturbation of the mitochondrial respiration. Conclusion Our results support the fact that DMD-inducing DCM can be modelled in the dish using patient-specific hiPSC-CMs. Such modelling may provide a better understanding of the pathophysiological mechanisms and the pharmacological treatment of the DMD-induced DCM. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/eurheartj/ehz748.0900 |
| الاتاحة: | http://dx.doi.org/10.1093/eurheartj/ehz748.0900 http://academic.oup.com/eurheartj/article-pdf/40/Supplement_1/ehz748.0900/30202985/ehz748.0900.pdf |
| Rights: | https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model |
| رقم الانضمام: | edsbas.292D8525 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/eurheartj/ehz748.0900 |
|---|