RESUMEN
A five-year-old boy was diagnosed with the ventricular septal rupture and ventricular aneurysm after blunt chest trauma in child abuse. Because of the intractable heart failure, he underwent operation in subacute period. Postoperative course was uneventful. The blunt cardiac injury in children can be caused by mild trauma and can be lethal. Surgical intervention should be considered when the clinical condition is unstable.
Asunto(s)
Aneurisma Cardíaco , Insuficiencia Cardíaca , Traumatismos Torácicos , Rotura Septal Ventricular , Heridas no Penetrantes , Preescolar , Humanos , Masculino , Aneurisma Cardíaco/diagnóstico por imagen , Aneurisma Cardíaco/etiología , Aneurisma Cardíaco/cirugía , Insuficiencia Cardíaca/etiología , Traumatismos Torácicos/complicaciones , Traumatismos Torácicos/diagnóstico por imagen , Rotura Septal Ventricular/diagnóstico por imagen , Rotura Septal Ventricular/etiología , Rotura Septal Ventricular/cirugía , Heridas no Penetrantes/complicaciones , Heridas no Penetrantes/diagnóstico por imagenRESUMEN
BACKGROUND: Duchenne muscular dystrophy (DMD), a severe degenerative skeletal and cardiac muscle disease, has a poor prognosis, and no curative treatments are available. Because decreased autophagy has been reported to contribute to skeletal muscle degeneration, therapies targeting autophagy are expected to improve skeletal muscle hypofunction. However, the role of this regulatory mechanism has not been evaluated clearly in DMD cardiomyocytes. METHODS: In this present study, we evaluated myocardial fibrosis and its mechanism in mdx mice, a model of DMD, and also evaluated changes in cardiac function. RESULTS: As assessed by LC3 immunohistochemistry, a small number of autophagosomes were detected in cardiomyocytes of both mdx mice and control wild-type (WT) mice. The number of autophagosomes was significantly enhanced by 4 weeks of isoproterenol-induced cardiac stress in cardiomyocytes of mdx but not WT mice. Simultaneously, isoproterenol increased cardiomyocyte fibrosis in mdx but not WT mice. Administration of chloroquine significantly decreased cardiomyocyte fibrosis in mdx mice, even after isoproterenol treatment. Left ventricle size and function were evaluated by echocardiography. Left ventricular contraction was decreased in mdx mice after isoproterenol treatment compared with control mice, which was alleviated by chloroquine administration. CONCLUSIONS: Heart failure in DMD patients is possibly treated with chloroquine, and the mechanism probably involves chloroquine's anti-inflammatory effects.
Asunto(s)
Cardiomiopatías , Distrofia Muscular de Duchenne , Humanos , Ratones , Animales , Distrofia Muscular de Duchenne/patología , Ratones Endogámicos mdx , Isoproterenol/farmacología , Músculo Esquelético , Miocitos Cardíacos/patología , Fibrosis , Modelos Animales de Enfermedad , DistrofinaRESUMEN
HOIL-1L deficiency was recently reported to be one of the causes of myopathy and dilated cardiomyopathy (DCM). However, the mechanisms by which myopathy and DCM develop have not been clearly elucidated. Here, we sought to elucidate these mechanisms using the murine myoblast cell line C2C12 and disease-specific human induced pluripotent stem cells (hiPSCs). Myotubes differentiated from HOIL-1L-KO C2C12 cells exhibited deteriorated differentiation and mitotic cell accumulation. CMs differentiated from patient-derived hiPSCs had an abnormal morphology with a larger size and were excessively multinucleated compared with CMs differentiated from control hiPSCs. Further analysis of hiPSC-derived CMs showed that HOIL-1L deficiency caused cell cycle alteration and mitotic cell accumulation. These results demonstrate that abnormal cell maturation possibly contribute to the development of myopathy and DCM. In conclusion, HOIL-1L is an important intrinsic regulator of cell cycle-related myotube and CM maturation and cell proliferation.