RESUMEN
Dilated cardiomyopathy (DCM) is the most frequent cause of heart failure and the leading indication for heart transplantation. Here we show that epigenetic regulator and central transcriptional instructor in adult stem cells, Bmi1, protects against DCM by repressing cardiac senescence. Cardiac-specific Bmi1 deletion induces the development of DCM, which progresses to lung congestion and heart failure. In contrast, Bmi1 overexpression in the heart protects from hypertrophic stimuli. Transcriptome analysis of mouse and human DCM samples indicates that p16(INK4a) derepression, accompanied by a senescence-associated secretory phenotype (SASP), is linked to severely impaired ventricular dimensions and contractility. Genetic reduction of p16(INK4a) levels reverses the pathology of Bmi1-deficient hearts. In parabiosis assays, the paracrine senescence response underlying the DCM phenotype does not transmit to healthy mice. As senescence is implicated in tissue repair and the loss of regenerative potential in aging tissues, these findings suggest a source for cardiac rejuvenation.
Asunto(s)
Envejecimiento/metabolismo , Cardiomiopatía Dilatada/metabolismo , Epigénesis Genética , Insuficiencia Cardíaca/metabolismo , Miocardio/metabolismo , Complejo Represivo Polycomb 1/genética , Envejecimiento/patología , Animales , Cardiomiopatía Dilatada/inducido químicamente , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/patología , Senescencia Celular , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Embrión de Mamíferos , Femenino , Regulación del Desarrollo de la Expresión Génica , Insuficiencia Cardíaca/inducido químicamente , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/patología , Ventrículos Cardíacos/metabolismo , Ventrículos Cardíacos/patología , Humanos , Isoproterenol , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Contracción Miocárdica/genética , Miocardio/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Comunicación Paracrina , Complejo Represivo Polycomb 1/metabolismo , TranscriptomaRESUMEN
Primary malignant melanoma of the esophagus is very rare, and only 139 cases have been described in all the world literature. We present one case of primary malignant melanoma of the esophagus in a 76-year-old woman who reported the symptoms of dysphagia and recent weight loss; the radiography showed a large polypoid mass filling the entire lower half of the esophagus, dark brown-black in the endoscopy. Histologic analysis demonstrated the existence of a malignant melanoma infiltrating the esophageal mucosa, composed of anaplastic cells with abundant brown pigment which had positive immunoreactivity for the S-100 protein.
