Asunto(s)
Ainhum/genética , Constricción Patológica/genética , Queratodermia Palmoplantar/genética , Mutación Missense/genética , Canales Catiónicos TRPV/genética , Administración Tópica , Adulto , Ainhum/diagnóstico , Ainhum/patología , Biopsia , Constricción Patológica/diagnóstico , Constricción Patológica/patología , Cuba/epidemiología , Femenino , Humanos , Queratodermia Palmoplantar/diagnóstico , Queratodermia Palmoplantar/tratamiento farmacológico , Queratodermia Palmoplantar/patología , Ácido Láctico/administración & dosificación , Ácido Láctico/uso terapéutico , Linaje , Canales Catiónicos TRPV/metabolismo , Urea/administración & dosificación , Urea/uso terapéuticoRESUMEN
OBJECTIVE: This study investigated the role of oxidative damage and nitric oxide (NO) synthases in the fetal heart using a model of intrauterine growth restriction induced by uteroplacental circulation restriction (UCR). METHODS: New Zealand white rabbits kept under 12-h light cycles, with food and water provided ad libitum, were subjected at day 25 of pregnancy to 40-50% uteroplacental artery ligation. We analyzed the gene expression of enzymes linked to nitric oxide synthesis (iNOS, eNOS, HO-1, and ARG-2), hypoxia inducible factor 1 alpha (HIF-1α), and the state of oxidative stress (protein carbonyl levels) in fetal heart homogenates. Additionally, we studied the histological morphology of the fetal heart. RESULTS: We found that fetal growth restriction was associated with a significant reduction in heart weight but a normal heart/body weight ratio in UCR animals. Hematoxylin and eosin staining showed normal left and right ventricular thickness but increased vessel dilatation with hyperemia in the hearts of the UCR group. We observed HIF-1α, eNOS, p-eNOS, and iNOS induction concomitant with intensified protein carbonyl levels but observed no changes in HO-1 or ARG-2 expression, suggesting increased NO and oxidative stress in the hearts of UCR animals. CONCLUSION: Uteroplacental circulation restriction increased NO-linked enzymes, oxidative damage, and dilated coronary vessels in fetal hearts. © 2017 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.
Asunto(s)
Retardo del Crecimiento Fetal , Corazón Fetal/metabolismo , Corazón Fetal/patología , Óxido Nítrico Sintasa/genética , Estrés Oxidativo/fisiología , Circulación Placentaria , Animales , Constricción Patológica/genética , Constricción Patológica/metabolismo , Constricción Patológica/patología , Estenosis Coronaria/genética , Estenosis Coronaria/metabolismo , Estenosis Coronaria/patología , Inducción Enzimática , Femenino , Retardo del Crecimiento Fetal/genética , Retardo del Crecimiento Fetal/patología , Regulación del Desarrollo de la Expresión Génica , Embarazo , ConejosRESUMEN
Hypertrophy is a major predictor of progressive heart disease and has an adverse prognosis. MicroRNAs (miRNAs) that accumulate during the course of cardiac hypertrophy may participate in the process. However, the nature of any interaction between a hypertrophy-specific signaling pathway and aberrant expression of miRNAs remains unclear. In this study, Spague Dawley male rats were treated with transverse aortic constriction (TAC) surgery to mimic pathological hypertrophy. Hearts were isolated from TAC and sham operated rats (n=5 for each group at 5, 10, 15, and 20 days after surgery) for miRNA microarray assay. The miRNAs dysexpressed during hypertrophy were further analyzed using a combination of bioinformatics algorithms in order to predict possible targets. Increased expression of the target genes identified in diverse signaling pathways was also analyzed. Two sets of miRNAs were identified, showing different expression patterns during hypertrophy. Bioinformatics analysis suggested the miRNAs may regulate multiple hypertrophy-specific signaling pathways by targeting the member genes and the interaction of miRNA and mRNA might form a network that leads to cardiac hypertrophy. In addition, the multifold changes in several miRNAs suggested that upregulation of rno-miR-331*, rno-miR-3596b, rno-miR-3557-5p and downregulation of rno-miR-10a, miR-221, miR-190, miR-451 could be seen as biomarkers of prognosis in clinical therapy of heart failure. This study described, for the first time, a potential mechanism of cardiac hypertrophy involving multiple signaling pathways that control up- and downregulation of miRNAs. It represents a first step in the systematic discovery of miRNA function in cardiovascular hypertrophy.
Asunto(s)
Animales , Masculino , Cardiomegalia/genética , Regulación hacia Abajo/genética , MicroARNs/metabolismo , Miocitos Cardíacos/patología , Transducción de Señal/genética , Regulación hacia Arriba/genética , Algoritmos , Aorta/cirugía , Biomarcadores , Biología Computacional , Constricción Patológica/genética , Modelos Animales de Enfermedad , Pronóstico , Ratas Sprague-DawleyRESUMEN
Hypertrophy is a major predictor of progressive heart disease and has an adverse prognosis. MicroRNAs (miRNAs) that accumulate during the course of cardiac hypertrophy may participate in the process. However, the nature of any interaction between a hypertrophy-specific signaling pathway and aberrant expression of miRNAs remains unclear. In this study, Spague Dawley male rats were treated with transverse aortic constriction (TAC) surgery to mimic pathological hypertrophy. Hearts were isolated from TAC and sham operated rats (n=5 for each group at 5, 10, 15, and 20 days after surgery) for miRNA microarray assay. The miRNAs dysexpressed during hypertrophy were further analyzed using a combination of bioinformatics algorithms in order to predict possible targets. Increased expression of the target genes identified in diverse signaling pathways was also analyzed. Two sets of miRNAs were identified, showing different expression patterns during hypertrophy. Bioinformatics analysis suggested the miRNAs may regulate multiple hypertrophy-specific signaling pathways by targeting the member genes and the interaction of miRNA and mRNA might form a network that leads to cardiac hypertrophy. In addition, the multifold changes in several miRNAs suggested that upregulation of rno-miR-331*, rno-miR-3596b, rno-miR-3557-5p and downregulation of rno-miR-10a, miR-221, miR-190, miR-451 could be seen as biomarkers of prognosis in clinical therapy of heart failure. This study described, for the first time, a potential mechanism of cardiac hypertrophy involving multiple signaling pathways that control up- and downregulation of miRNAs. It represents a first step in the systematic discovery of miRNA function in cardiovascular hypertrophy.
Asunto(s)
Cardiomegalia/genética , Regulación hacia Abajo/genética , MicroARNs/metabolismo , Miocitos Cardíacos/patología , Transducción de Señal/genética , Regulación hacia Arriba/genética , Algoritmos , Animales , Aorta/cirugía , Biomarcadores , Biología Computacional , Constricción Patológica/genética , Modelos Animales de Enfermedad , Masculino , Pronóstico , Ratas Sprague-DawleyRESUMEN
In this study, we have identified and evaluated the cardiovascular anomalies associated with Williams-Beuren syndrome in children.In a retrospective, lineal, and observational study, we reviewed the files of children who were seen from 1980 through 2005 (25 years) after a clinical diagnosis of Williams-Beuren syndrome.Forty children were diagnosed with this syndrome at the National Institute of Pediatrics in Mexico City. Of these, 32 (80%) were found to have congenital heart defects. The male-to-female ratio was 1.3:1 and ages ranged from 6 months to 15 years (mean, 4.4 years) at the time of diagnosis. All of the patients had morphologic and genetic characteristics typical of the syndrome.We emphasize the cardiovascular aspects from a clinical point of view. Supravalvular aortic stenosis was our most frequent finding, in 18 of 32 patients (56%); gradient differences in these patients ranged from 14 to 81 mmHg. Five patients showed combined lesions, the most frequent being supravalvular aortic stenosis in combination with pulmonary artery brachial stenosis, or with atrial and ventricular defects. Patients with incomplete atrioventricular defect and bicuspid aortic valve, as were seen at our hospital, have not to our knowledge been reported in other studies.One of the patients was scheduled for balloon dilation; another was scheduled for surgery; a 3rd patient was operated on twice for the placement of an aorto-aortic bridge; another underwent ventricular septal defect closure; and yet another underwent aortoplasty, this last dying shortly after surgery.