Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.724
Filtrar
1.
J Forensic Sci ; 65(1): 117-127, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31404479

RESUMO

Sudden cardiac death is a significant cause of mortality in adults with congenital heart disease (CHD). The Cook County Medical Examiner's Office database was queried for cases of CHD as a cause of death in the period between July 2008 and April 2019. Twenty-two cases were identified, including 11 decedents with simple defects and 10 decedents with complex defects. All of the subjects were in apparent good health at the time of death. In the absence of other obvious causes of death, simple defects were considered cases of sudden cardiac death. Significant cardiac morphological changes were common in complex defects. While 16 cases had known, diagnosed/treated CHD, 5 cases had no diagnosis prior to autopsy. In these cases, the ability to recognize CHD (sometimes subtle) helped in determining the causes of death. Therefore, forensic pathologists must be able to properly recognize various forms of CHD and request consultations, when needed.


Assuntos
Morte Súbita Cardíaca/epidemiologia , Cardiopatias Congênitas/mortalidade , Cardiopatias Congênitas/patologia , Adulto , Distribuição por Idade , Idoso , Cardiomegalia/patologia , Chicago/epidemiologia , Médicos Legistas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Distribuição por Sexo , Adulto Jovem
2.
Braz J Cardiovasc Surg ; 34(5): 637-639, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31719017

RESUMO

Quadricuspid aortic valve (QAV) is a rare cardiac malformation. Many cases are incidentally diagnosed in aortic surgeries or autopsies and it usually appears as an isolated anomaly. The most widely classification used is the one by Hurwitz and Roberts[], which divides 7 alphabetical subtypes based on the cusps size. The aim of this report is to describe three different anatomic presentations of this rare aortic valve anomaly.


Assuntos
Valva Aórtica/anormalidades , Valva Aórtica/patologia , Cardiopatias Congênitas/patologia , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Ecocardiografia , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/cirurgia , Implante de Prótese de Valva Cardíaca/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
3.
Nat Commun ; 10(1): 4722, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31624253

RESUMO

The genetic architecture of sporadic congenital heart disease (CHD) is characterized by enrichment in damaging de novo variants in chromatin-modifying genes. To test the hypothesis that gene pathways contributing to de novo forms of CHD are distinct from those for recessive forms, we analyze 2391 whole-exome trios from the Pediatric Cardiac Genomics Consortium. We deploy a permutation-based gene-burden analysis to identify damaging recessive and compound heterozygous genotypes and disease genes, controlling for confounding effects, such as background mutation rate and ancestry. Cilia-related genes are significantly enriched for damaging rare recessive genotypes, but comparatively depleted for de novo variants. The opposite trend is observed for chromatin-modifying genes. Other cardiac developmental gene classes have less stratification by mode of inheritance than cilia and chromatin-modifying gene classes. Our analyses reveal dominant and recessive CHD are associated with distinct gene functions, with cilia-related genes providing a reservoir of rare segregating variation leading to CHD.


Assuntos
Genes Dominantes , Genes Recessivos , Predisposição Genética para Doença/genética , Cardiopatias Congênitas/genética , Mutação , Estudos de Casos e Controles , Criança , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Cardiopatias Congênitas/patologia , Humanos , Masculino , Fenótipo , Sequenciamento Completo do Exoma
4.
Autops. Case Rep ; 9(3): e2019118, July-Sept. 2019. ilus
Artigo em Inglês | LILACS | ID: biblio-1017367

RESUMO

Acute obstruction of superior vena cava anastomosis right after the Glenn procedure may lead to tragic consequences. We describe the case of a one-year-old child with tricuspid atresia and a previous Blalock-Taussig shunt procedure, who presented severe low cardiac output syndrome right after the Glenn procedure and died forty-four hours after the procedure. The autopsy showed obstruction of the superior vena cava anastomosis. Patients that present superior vena cava syndrome and low cardiac output right after the Glenn procedure should have the surgical anastomosis revised immediately.


Assuntos
Humanos , Feminino , Recém-Nascido , Derivação Cardíaca Direita , Técnica de Fontan/efeitos adversos , Cardiopatias Congênitas/patologia , Autopsia , Evolução Fatal , Atresia Tricúspide/complicações , Procedimento de Blalock-Taussig/efeitos adversos
5.
J Pediatr Endocrinol Metab ; 32(8): 797-802, 2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31323007

RESUMO

PHACE syndrome is an uncommon disorder of posterior fossa anomalies, cervicofacial infantile hemangiomas, arterial anomalies, cardiac defects, eye anomalies, and midline/ventral defects. Endocrine abnormalities including hypopituitarism and ectopic thyroid were rarely described. In this article we review occurrence, onset, presenting symptoms, hormonal treatments and outcomes of all endocrine abnormalities in PHACE syndrome. Eleven of 20 (55%) had hypothalamic-pituitary dysfunction and 10 of 20 (50%) had thyroid dysgenesis. A thorough understanding of the endocrine manifestations is important for clinicians to early identify endocrine involvement in PHACE and develop plans for monitoring and treatment of its complications.


Assuntos
Anormalidades Múltiplas/etiologia , Coartação Aórtica/etiologia , Doenças do Sistema Endócrino/complicações , Anormalidades do Olho/etiologia , Síndromes Neurocutâneas/etiologia , Anormalidades Múltiplas/patologia , Coartação Aórtica/patologia , Fossa Craniana Posterior/patologia , Anormalidades do Olho/patologia , Neoplasias Faciais/etiologia , Neoplasias Faciais/patologia , Cardiopatias Congênitas/etiologia , Cardiopatias Congênitas/patologia , Hemangioma/etiologia , Hemangioma/patologia , Humanos , Síndromes Neurocutâneas/patologia , Síndrome
6.
Handb Clin Neurol ; 162: 329-345, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31324319

RESUMO

Congenital heart disease (CHD) constitutes the most common congenital malformation, with moderate or severe CHD occurring in around 6 in 1000 live births. Due to advances in medical care, survival rates have increased significantly. Thus, the majority of children with CHD survive until adolescence and adulthood. Children with CHD requiring cardiopulmonary bypass surgery are at risk for neurodevelopmental impairments in various domains, including mild impairments in cognitive and neuromotor functions, difficulties with social interaction, inattention, emotional symptoms, and impaired executive function. The prevalence for these impairments ranges from 20% to 60% depending on age and domain ("high prevalence-low severity"). Domains are often affected simultaneously, leading to school problems with the need for learning support and special interventions. The etiology of neurodevelopmental impairments is complex, consisting of a combination of delayed intrauterine brain development and newly occurring perioperative brain injuries. Mechanisms include altered intrauterine hemodynamic flow as well as neonatal hypoxia and reduced cerebral blood flow. The surgical procedure and postoperative phase add to this cascade of factors interfering with normal brain development. Early identification of children at high risk through structured follow-up programs is mandated to provide individually tailored early interventions and counseling to improve developmental health.


Assuntos
Desenvolvimento Infantil , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/patologia , Adolescente , Adulto , Deficiências do Desenvolvimento/etiologia , Deficiências do Desenvolvimento/psicologia , Deficiências do Desenvolvimento/terapia , Feminino , Cardiopatias Congênitas/psicologia , Cardiopatias Congênitas/cirurgia , Humanos , Recém-Nascido , Gravidez , Adulto Jovem
7.
Nature ; 572(7767): 120-124, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31341279

RESUMO

Organogenesis involves integration of diverse cell types; dysregulation of cell-type-specific gene networks results in birth defects, which affect 5% of live births. Congenital heart defects are the most common malformations, and result from disruption of discrete subsets of cardiac progenitor cells1, but the transcriptional changes in individual progenitors that lead to organ-level defects remain unknown. Here we used single-cell RNA sequencing to interrogate early cardiac progenitor cells as they become specified during normal and abnormal cardiogenesis, revealing how dysregulation of specific cellular subpopulations has catastrophic consequences. A network-based computational method for single-cell RNA-sequencing analysis that predicts lineage-specifying transcription factors2,3 identified Hand2 as a specifier of outflow tract cells but not right ventricular cells, despite the failure of right ventricular formation in Hand2-null mice4. Temporal single-cell-transcriptome analysis of Hand2-null embryos revealed failure of outflow tract myocardium specification, whereas right ventricular myocardium was specified but failed to properly differentiate and migrate. Loss of Hand2 also led to dysregulation of retinoic acid signalling and disruption of anterior-posterior patterning of cardiac progenitors. This work reveals transcriptional determinants that specify fate and differentiation in individual cardiac progenitor cells, and exposes mechanisms of disrupted cardiac development at single-cell resolution, providing a framework for investigating congenital heart defects.


Assuntos
Cardiopatias Congênitas/embriologia , Cardiopatias Congênitas/patologia , Coração/embriologia , Análise de Célula Única , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/deficiência , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Diferenciação Celular , Movimento Celular , Análise por Conglomerados , Feminino , Cardiopatias Congênitas/genética , Masculino , Camundongos , Análise de Sequência de RNA , Tretinoína/metabolismo
8.
Cytogenet Genome Res ; 158(3): 121-125, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31315107

RESUMO

VACTERL association is defined by the occurrence of congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula with esophageal atresia, radial and renal dysplasia, and limb defects. No genetic alterations have been discovered except for some sporadic chromosomal rearrangements and gene mutations. We report a boy with VACTERL association and shawl scrotum with bifid scrotum who presented with a de novo Yq11.223q11.23 microdeletion identified by array CGH. The deletion spans 3.1 Mb and encompasses several genes in the AZFc region, frequently deleted in infertile men with severe oligozoospermia or azoospermia. Herein, we discuss the possible explanation for this unusual genotype-phenotype correlation. We suggest that the deletion of the BPY2 (previously VCY2) gene, located in the AZFc region and involved in spermatogenesis, contributed to the genesis of the phenotype. In fact, BPY2 interacts with a ubiquitin-protein ligase, involved in the SHH pathway which is known to be implicated in the genesis of VACTERL association.


Assuntos
Canal Anal/anormalidades , Deleção Cromossômica , Cromossomos Humanos Y/genética , Esôfago/anormalidades , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/patologia , Rim/anormalidades , Deformidades Congênitas dos Membros/genética , Deformidades Congênitas dos Membros/patologia , Proteínas/genética , Escroto/patologia , Coluna Vertebral/anormalidades , Traqueia/anormalidades , Canal Anal/patologia , Hibridização Genômica Comparativa , Esôfago/patologia , Estudos de Associação Genética , Humanos , Lactente , Rim/patologia , Masculino , Coluna Vertebral/patologia , Traqueia/patologia , Ubiquitina-Proteína Ligases/metabolismo , Incerteza
9.
J Hum Genet ; 64(9): 885-890, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31270375

RESUMO

Pediatric hypertension can cause hypertensive emergencies, including hemorrhagic stroke, contributing to rare but serious childhood morbidity and mortality. Renovascular hypertension (RVH) is one of the major causes of secondary hypertension in children. Grange syndrome (MIM#602531) is a rare disease characterized by multiple stenosis or occlusion of the renal, abdominal, coronary, and cerebral arteries, which can cause phenotypes of RVH and fibromuscular dysplasia (MIM#135580). We report the case of a 7-year-old girl with Grange syndrome who showed RVH and multiple seizure episodes. At 1 year of age, she experienced seizures and sequential hemiparesis caused by a left thalamic hemorrhage without cerebral vascular anomalies. Chronic hypertension was observed, and abdominal computed tomography angiography showed characteristic bilateral renal artery stenosis. Whole-exome sequencing revealed a novel homozygous pathogenic variant in the YY1AP1 gene (NM_001198903.1: c.1169del: p.Lys390Argfs*12). Biallelic YY1AP1 mutations are known to cause Grange syndrome. Unlike previously reported patients, our patient presented with intracerebral hemorrhagic stroke without anomalous brain artery or bone fragility. The phenotype in our patient may help better understand this ultra-rare syndrome. Grange syndrome should be considered in patients presenting with childhood-onset hypertension and/or hemorrhagic stroke for early clinical intervention.


Assuntos
Sequência de Aminoácidos , Arteriopatias Oclusivas/genética , Osso e Ossos/anormalidades , Braquidactilia/genética , Proteínas de Ciclo Celular/genética , Cardiopatias Congênitas/genética , Hipertensão Renovascular/genética , Hipertensão/genética , Hemorragias Intracranianas/genética , Deleção de Sequência , Acidente Vascular Cerebral/genética , Sindactilia/genética , Fatores de Transcrição/genética , Arteriopatias Oclusivas/patologia , Arteriopatias Oclusivas/fisiopatologia , Osso e Ossos/patologia , Osso e Ossos/fisiopatologia , Braquidactilia/patologia , Braquidactilia/fisiopatologia , Criança , Feminino , Cardiopatias Congênitas/patologia , Cardiopatias Congênitas/fisiopatologia , Homozigoto , Humanos , Hipertensão/patologia , Hipertensão/fisiopatologia , Hipertensão Renovascular/patologia , Hipertensão Renovascular/fisiopatologia , Hemorragias Intracranianas/patologia , Hemorragias Intracranianas/fisiopatologia , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/fisiopatologia , Sindactilia/patologia , Sindactilia/fisiopatologia
10.
Life Sci ; 232: 116635, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31283925

RESUMO

AIMS: The pathological cardiac hypertrophy will develop into heart failure, which has no effective treatment currently. Previous studies have proved that microRNAs (miRNAs) participate in the development of cardiac hypertrophy and regulate the pathological progress. In this study, we want to investigate the role of microRNA-92b-3p (miR-92b-3p) in cardiomyocyte hypertrophy and the mechanisms involved. MATERIALS AND METHODS: Neonatal mouse ventricular cells (NMVCs) were isolated from the hearts of 1-3-d-old newborn C57BL6 mice. The isolated NMVCs were induced hypertrophic phenotype by Angiotensin-II (Ang-II) and the cell size was examined by FITC-phalloidin staining assay. The expression of miR-92b-3p was determined by quantitative real-time PCR (qRT-qPCR). MRNA and protein level of ß-MHC, ACTA1 and HAND2 in NMVCs transfected with miR-92b-3p mimic and inhibition were assessed by RT-qPCR assay and western blot assay, respectively. Dual luciferase assay was used to verify the interaction between miR-92b-3p and the 3'-untranslated region (UTR) of HAND2 gene. KEY FINDINGS: MiR-92b-3p and HAND2 were significantly increased in Ang-II-induced NMVCs. Overexpression of miR-92b-3p can ameliorate Ang-II-induced cardiomyocyte hypertrophy. MiR-92b-3p negatively regulated HAND2 expression at the transcriptional level. Both miR-92b-3p mimic and HAND2 siRNA could efficiently inhibit Ang-II-induced hypertrophy in mouse cardiomyocytes. SIGNIFICANCE: MiR-92b-3p inhibits Ang-II-induced cardiomyocyte hypertrophy via targeting HAND2.


Assuntos
Angiotensina II/farmacologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Cardiomiopatia Hipertrófica/tratamento farmacológico , Cardiomiopatia Hipertrófica/metabolismo , MicroRNAs/metabolismo , Miócitos Cardíacos/patologia , Regiões 3' não Traduzidas , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/patologia , Modelos Animais de Doenças , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/metabolismo , Cardiopatias Congênitas/patologia , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Ventrículos do Coração/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima
11.
Histochem Cell Biol ; 152(3): 217-225, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31197456

RESUMO

Gestational diabetes mellitus is a risk factor for congenital heart defects. Our previous results indicated that a decrease in myocardial cells and an increase in apoptotic cells leads to heart defects under hyperglycemia, but much work remains to elucidate this important mechanism of myocardial cell apoptosis induced by high glucose (HG). In this study, we found that a decrease in GSK3ß phosphorylation on Ser9 occurred concomitantly with HG-induced cardiomyocyte apoptosis and in the heart tissues of the offspring of diabetic rats in vitro and in vivo. Decreases in GSK3ß (Ser9) phosphorylation in response to HG were remarkably restored after treatment with SC79, an activator of the Akt signaling pathway. SB216763, an effective inhibitor of the GSK3ß signaling pathway, suppressed HG-induced apoptosis in cardiomyocytes. Further studies showed a decrease in the expression of the anti-apoptotic protein MCL-1 was associated with GSK3ß-mediated apoptosis. MCL-1 overexpression partly inhibits HG-induced apoptosis in cardiomyocytes. Herein, this study revealed the roles of GSK3ß and MCL-1 in modulating HG-induced cardiomyocyte apoptosis and maternal diabetes-induced abnormalities.


Assuntos
Apoptose , Glicemia/metabolismo , Diabetes Gestacional/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Cardiopatias Congênitas/metabolismo , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Células Cultivadas , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Gestacional/patologia , Feminino , Cardiopatias Congênitas/patologia , Masculino , Miócitos Cardíacos/patologia , Fosforilação , Gravidez , Ratos , Ratos Sprague-Dawley
12.
Pediatr Cardiol ; 40(6): 1258-1265, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31240370

RESUMO

The most common modes of medical education for congenital heart disease (CHD) rely heavily on 2-dimensional imaging. Three-dimensional (3D) printing technology allows for the creation of physical cardiac models that can be used for teaching trainees. 3D printed cardiac models were created for the following lesions: pulmonic stenosis, atrial septal defect, tetralogy of Fallot, d-transposition of the great arteries, coarctation of the aorta, and hypoplastic left heart syndrome. Medical students participated in a workshop consisting of different teaching stations. At the 3D printed station, students completed a pre- and post-intervention survey assessing their knowledge of each cardiac lesion on a Likert scale. Students were asked to rank the educational benefit of each modality. Linear regression was utilized to assess the correlation of the mean increase in knowledge with increasing complexity of CHD based on the Aristotle Basic Complexity Level. 45 medical students attended the CHD workshop. Students' knowledge significantly improved for every lesion (p < 0.001). A strong positive correlation was found between mean increase in knowledge and increasing complexity of CHD (R2 = 0.73, p < 0.05). The 3D printed models, pathology specimens and spoken explanation were found to be the most helpful modalities. Students "strongly agreed" the 3D printed models made them more confident in explaining congenital cardiac anatomy to others (mean = 4.23, ± 0.69), and that they recommend the use of 3D models for future educational sessions (mean = 4.40, ± 0.69). 3D printed cardiac models should be included in medical student education particularly for lesions that require a complex understanding of spatial relationships.


Assuntos
Educação Médica/métodos , Cardiopatias Congênitas/patologia , Modelos Anatômicos , Impressão Tridimensional , Adulto , Feminino , Cardiopatias Congênitas/diagnóstico por imagem , Humanos , Masculino , Autorrelato , Estudantes de Medicina/estatística & dados numéricos , Adulto Jovem
13.
J Med Case Rep ; 13(1): 184, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31203815

RESUMO

BACKGROUND: Accessory mitral valve tissue is a rare congenital anomaly that is commonly diagnosed in early childhood and rarely in adulthood. It is usually asymptomatic. However, it may cause left ventricular outflow tract obstruction in a way that mimics various other causes of obstruction. A 72-year-old Caucasian man complained of chest discomfort and exertional dyspnea for 3 months. There were no specific findings from a physical examination except systolic murmur. Transthoracic echocardiography demonstrated a mass on the mitral valve extending to the intraventricular septal, raising the pressure gradient flow across the aortic valve. Transesophageal echocardiography showed parachute-like tissue connected to the anterior leaflet of the mitral valve causing left ventricular outflow tract obstruction. During the surgery preparation period, he underwent coronary angiography and computed tomography to study the anatomy surrounding the mass. After surgery, biopsy showed non-specific findings. CONCLUSION: When facing a case of aortic valve stenosis, accessory mitral valve tissue should be kept in mind as one of the possible underlying causes despite its rarity. Although it is simple and noninvasive, echocardiography remains the best diagnostic procedure to make the correct decision about management and to define the golden time for surgical intervention.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Cardiopatias Congênitas , Valva Mitral , Obstrução do Fluxo Ventricular Externo , Idoso , Angiografia Coronária/métodos , Ecocardiografia Transesofagiana/métodos , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/patologia , Cardiopatias Congênitas/fisiopatologia , Humanos , Masculino , Valva Mitral/diagnóstico por imagem , Valva Mitral/patologia , Valva Mitral/fisiopatologia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Obstrução do Fluxo Ventricular Externo/diagnóstico , Obstrução do Fluxo Ventricular Externo/etiologia , Obstrução do Fluxo Ventricular Externo/fisiopatologia , Obstrução do Fluxo Ventricular Externo/cirurgia
14.
Med. infant ; 26(2): 156-167, Junio 2019. ilus
Artigo em Espanhol | LILACS | ID: biblio-1016616

RESUMO

Las cardiopatías congénitas presentan con frecuencia patrones anatómicos complejos y tradicionalmente se han estudiado con ecocardiografía y eventualmente con cateterismo cardíaco. Con los avances tecnológicos de las últimas décadas, la tomografía computada y la resonancia magnética nuclear han adquirido gran importancia en la evaluación cardíaca. Actualmente constituyen métodos utilizados en el estudio de variadas patologías cardiovasculares de la infancia de difícil diagnóstico ecográfico, que previamente eran evaluadas por angiografía convencional, lo cual implicaba una dosis de radiación mucho mayor (AU)


Congenital heart defects often have complex anatomical patterns and have traditionally been studied with echocardiography and eventually cardiac catheterization. With technological advances in recent decades, computed tomography and magnetic resonance imaging have become very important in cardiac evaluation. Currently, they are the methods of choice in the study of a wide range of childhood cardiovascular diseases that are difficult to diagnose with echocardiography, which were previously evaluated using conventional angiography, involving a much higher dose of radiation (AU)


Assuntos
Humanos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Imagem por Ressonância Magnética , Tomografia Computadorizada Multidetectores , Angiografia por Tomografia Computadorizada , Coração/diagnóstico por imagem , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/patologia
15.
PLoS One ; 14(5): e0216477, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31141530

RESUMO

BACKGROUND: Maternal hypertension, type 2 diabetes (T2D) and obesity are associated with an increased risk of having offspring with conotruncal heart defects (CTDs). Prior studies have identified sets of single nucleotide polymorphisms (SNPs) that are associated with risk for each of these three adult phenotypes. We hypothesized that these same SNPs are associated with maternal risk of CTDs in offspring. METHODS AND RESULTS: We evaluated the parents of children with a CTD ascertained from the Children's Hospital of Philadelphia (n = 466) and by the Pediatric Cardiac Genomic Consortium (n = 255). We used a family-based design to assess the association between CTDs and the maternal genotype for individual hypertension, T2D, and obesity-related SNPs and found no association between CTDs and the maternal genotype for any individual SNP. In addition, we calculated genetic risk scores (GRS) for hypertension, T2D, and obesity using previously published GRS formulas. When comparing the GRS of mothers to fathers, there were no statistically significant differences in the mean for the combined GRS or the GRS for each individual condition. However, when we categorized the mothers and fathers of cases with CTDs as having high (>95th percentile) or low (≤95th percentile) scores, compared to fathers, mothers had almost two times the odds of having a high GRS for hypertension (OR 1.7, 95% CI 1.0, 2.8) and T2D (OR 1.8, 95% CI 1.1, 3.1). CONCLUSIONS: Our results support a link between maternal genetic risk for hypertension/T2D and CTDs in their offspring. These associations might be independent of maternal phenotype at conception.


Assuntos
Diabetes Mellitus Tipo 2/genética , Cardiopatias Congênitas/genética , Hipertensão/genética , Polimorfismo de Nucleotídeo Único , Complicações Cardiovasculares na Gravidez/genética , Gravidez em Diabéticas/genética , Adulto , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Cardiopatias Congênitas/patologia , Cardiopatias Congênitas/fisiopatologia , Humanos , Hipertensão/patologia , Hipertensão/fisiopatologia , Masculino , /fisiopatologia , Gravidez , Complicações Cardiovasculares na Gravidez/patologia , Complicações Cardiovasculares na Gravidez/fisiopatologia , Gravidez em Diabéticas/patologia , Gravidez em Diabéticas/fisiopatologia , Fatores de Risco
16.
Angiology ; 70(10): 969-977, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31064194

RESUMO

Aortic diameter and progression to thoracic aortic aneurysm are influenced by several factors. In this study, we investigated the association of alcohol consumption with aortic root and ascending aorta dilatation. In the context of the Corinthia study, we examined 1751 patients with echocardiography. Several demographic and clinical characteristics were recorded. Alcohol consumption was assessed based on a questionnaire of frequency, type, and quantity. Accordingly, patients were categorized as everyday alcohol consumers (EDACs) and as social drinkers (SoD). Everyday alcohol consumers were further categorized to group 1: 0 to 1 drink/d; group 2: 1 to 2 drinks/d; and group 3: ≥3 drinks/d. From the study population, 40% were categorized as EDAC and had an increased aortic root diameter (AoRD) and an elevated AoRD index compared with SoD. Interestingly, there was a stepwise increase in aortic root and ascending aorta diameter according to daily alcohol consumption. Specifically, patients consuming ≥3 drinks of alcohol/d had increased indexed aortic by 1.4 mm/m2 compared with SoD even after adjustment for possible confounders. Daily alcohol consumption is associated with increased aortic root diameter. These findings may have important clinical implications, especially in patients with borderline or dilated aortic root, and merit further investigation.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Aorta Torácica/patologia , Doenças da Aorta/patologia , Cardiopatias Congênitas/patologia , Doenças das Valvas Cardíacas/patologia , Adulto , Idoso , Consumo de Bebidas Alcoólicas/metabolismo , Aorta Torácica/diagnóstico por imagem , Doenças da Aorta/fisiopatologia , Valva Aórtica/patologia , Valva Aórtica/fisiopatologia , Dilatação Patológica/patologia , Dilatação Patológica/fisiopatologia , Ecocardiografia Transesofagiana/métodos , Feminino , Cardiopatias Congênitas/fisiopatologia , Doenças das Valvas Cardíacas/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco
17.
PLoS One ; 14(5): e0214873, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31086358

RESUMO

BACKGROUNDS: Reducing toxicants transplacental rates could contribute to the prevention of congenital heart defects (CHDs). Placental P-glycoprotein (P-gp) plays a vital role in fetal toxicants exposure and subsequently affects the risk of toxicants-induced birth defects. However, data on the role of placental P-gp in decreasing toxicants-induced cardiac anomalies is extremely limited. This study aimed to explore the protective role of placental P-gp in reducing the risk of Di-(2-ethylhexyl)-phthalate (DEHP) induced cardiac anomalies in mice. METHODS: The C57BL mice were randomly divided into four groups: the vehicle group (corn oil, n = 10), 500mg/Kg DEHP group (n = 15), 3mg/Kg verapamil group (n = 10) and 500mg/Kg DEHP & 3mg/Kg verapamil group (n = 20). Pregnant dams in different group received respective intervention by gavage once daily from E6.5-14.5. Maternal weights were monitored every day and samples were collected at E15.5. HE staining was used to examine fetal cardiac malformations. Real-time quantitative PCR (RT-qPCR) and Western-Blot were applied to detect Nkx2.5/Gata4/Tbx5/Mef2c/Chf1 mRNA and protein expression, respectively. The mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ) was also determined using RT-qPCR. RESULTS: Co-administration of verapamil and DEHP significantly elevated fetal cardiac malformation rates, in comparison with the DEHP group, the verapamil group and the vehicle group. Different phenotypes of cardiac anomalies, including septal defects and ventricular myocardium noncompaction, were noted both in the DEHP group and the DEHP & verapamil group. The ventricular myocardium noncompaction appeared to be more severe in the DEHP & verapamil group. Fetal cardiac PPARγ mRNA expression was notably increased and Gata4/Mef2c/Chf1 expression was markedly decreased in the DEHP & verapamil group. CONCLUSION: Placental P-gp inhibition enhances susceptibility to DEHP induced cardiac malformations in mice.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Dietilexilftalato/toxicidade , Coração Fetal/efeitos dos fármacos , Cardiopatias Congênitas/patologia , Placenta/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Animais , Feminino , Coração Fetal/metabolismo , Coração Fetal/patologia , Fator de Transcrição GATA4/genética , Fator de Transcrição GATA4/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Cardiopatias Congênitas/induzido quimicamente , Cardiopatias Congênitas/metabolismo , Proteína Homeobox Nkx-2.5/genética , Proteína Homeobox Nkx-2.5/metabolismo , Exposição Materna , Camundongos , Camundongos Endogâmicos C57BL , PPAR gama/genética , PPAR gama/metabolismo , Gravidez , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo , Verapamil/farmacologia
18.
BMC Genomics ; 20(1): 386, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31101013

RESUMO

BACKGROUND: Adenovirus protein, Gam1, triggers the proteolytic destruction of the E1 SUMO-activating enzyme. Microinjection of an empirically determined amount of Gam1 mRNA into one-cell Xenopus embryos can reduce SUMOylation activity to undetectable, but nonlethal, levels, enabling an examination of the role of this post-translational modification during early vertebrate development. RESULTS: We find that SUMOylation-deficient embryos consistently exhibit defects in neural tube and heart development. We have measured differences in gene expression between control and embryos injected with Gam1 mRNA at three developmental stages: early gastrula (immediately following the initiation of zygotic transcription), late gastrula (completion of the formation of the three primary germ layers), and early neurula (appearance of the neural plate). Although changes in gene expression are widespread and can be linked to many biological processes, three pathways, non-canonical Wnt/PCP, snail/twist, and Ets-1, are especially sensitive to the loss of SUMOylation activity and can largely account for the predominant phenotypes of Gam1 embryos. SUMOylation appears to generate different pools of a given transcription factor having different specificities with this post-translational modification involved in the regulation of more complex, as opposed to housekeeping, processes. CONCLUSIONS: We have identified changes in gene expression that underlie the neural tube and heart phenotypes resulting from depressed SUMOylation activity. Notably, these developmental defects correspond to the two most frequently occurring congenital birth defects in humans, strongly suggesting that perturbation of SUMOylation, either globally or of a specific protein, may frequently be the origin of these pathologies.


Assuntos
Embrião de Mamíferos/patologia , Regulação da Expressão Gênica no Desenvolvimento , Cardiopatias Congênitas/genética , Defeitos do Tubo Neural/genética , Sumoilação , Proteínas de Xenopus/metabolismo , Animais , Embrião de Mamíferos/metabolismo , Feminino , Perfilação da Expressão Gênica , Cardiopatias Congênitas/patologia , Masculino , Defeitos do Tubo Neural/patologia , Proteínas Virais/administração & dosagem , Xenopus laevis
19.
Orphanet J Rare Dis ; 14(1): 76, 2019 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-30944003

RESUMO

BACKGROUND: Discussions continue as to whether ventricular septal defects are best categorized according to their right ventricular geography or their borders. This is especially true when considering the perimembranous defect. Our aim, therefore, was to establish the phenotypic feature of the perimembranous defect, and to establish the ease of distinguishing its geographical variants. METHODS AND RESULTS: We assessed unrepaired isolated perimembranous ventricular defects from six historic archives, subcategorizing them using the ICD-11 coding system. We identified 365 defects, of which 94 (26%) were deemed to open centrally, 168 (46%) to open to the outlet, and 84 (23%) to the inlet of the right ventricle, with 19 (5%) being confluent. In all hearts, the unifying phenotypic feature was fibrous continuity between the leaflets of the mitral and tricuspid valves. This was often directly between the valves, but in all instances incorporated continuity through the atrioventricular portion of the membranous septum. In contrast, we observed fibrous continuity between the leaflets of the tricuspid and aortic valves in only 298 (82%) of the specimens. When found, discontinuity most commonly was seen in the outlet and central defects. There were no discrepancies between evaluators in distinguishing the borders, but there was occasional disagreement in determining the right ventricular geography of the defect. CONCLUSIONS: The unifying feature of perimembranous defects, rather than being aortic-to-tricuspid valvar fibrous continuity, is fibrous continuity between the leaflets of the atrioventricular valves. While right ventricular geography is important in classification, it is the borders which are more objectively defined.


Assuntos
Comunicação Interventricular/patologia , Consenso , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/patologia , Comunicação Interventricular/diagnóstico , Humanos
20.
ACS Appl Mater Interfaces ; 11(20): 18242-18253, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31021079

RESUMO

Congenital heart disease is the number one cause of birth defect-related death because it often leads to right ventricular heart failure (RVHF). One promising avenue to combat this RVHF is the use of cardiac patches composed of stem cells and scaffolds. Herein, we demonstrate a reparative cardiac patch by combining neonatal or child c-kit+  progenitor cells (CPCs) with a scaffold composed of electrospun polycaprolactone nanofibers. We examined different parameters of the patch, including the alignment, composition, and surface properties of the nanofibers, as well as the age of the CPCs. The patch based on uniaxially aligned nanofibers successfully aligned the CPCs. With the inclusion of gelatin in the nanofiber matrix and/or coating of fibronectin on the surface of the nanofibers, the metabolism of both neonatal and child CPCs was generally enhanced. The conditioned media collected from both patches based on aligned and random nanofibers could reduce the fibrotic gene expression in rat cardiac fibroblasts, following stimulation with transforming growth factor ß. Furthermore, the conditioned media collected from the nanofiber-based patches could lead to the formation of tubes of human umbilical vein endothelial cells, indicating the pro-angiogenic capability of the patch. Taken together, the electrospun nanofiber-based patches are a suitable delivery vehicle for CPCs and can confer reparative benefit through anti-fibrotic and pro-angiogenic paracrine signaling.


Assuntos
Células Imobilizadas/metabolismo , Células Imobilizadas/transplante , Miocárdio/metabolismo , Nanofibras/química , Transplante de Células-Tronco , Células-Tronco/metabolismo , Animais , Células Imobilizadas/patologia , Pré-Escolar , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Cardiopatias Congênitas/metabolismo , Cardiopatias Congênitas/patologia , Cardiopatias Congênitas/terapia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Lactente , Recém-Nascido , Masculino , Miocárdio/patologia , Ratos , Células-Tronco/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA