Assuntos
Cardiomegalia/diagnóstico por imagem , Ecocardiografia Tridimensional/métodos , Coração Fetal/diagnóstico por imagem , Fístula/complicações , Fístula/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Adulto , Cardiomegalia/embriologia , Cardiomegalia/etiologia , Feminino , Fístula/embriologia , Átrios do Coração/diagnóstico por imagem , Humanos , Gravidez , Artéria Pulmonar/diagnóstico por imagemRESUMO
Twin to twin transfusion syndrome (TTTS) is a major complication of monochorionic diamniotic (MD) twins, and its onset is known to be associated with placental vascular anastomoses and blood flow imbalance. In a typical case of TTTS, the recipient develops polyhydramnios, weight gain, cardiomegaly and hydrops fetalis in the uterus. In contrast, the donor develops oligohydramnios and intrauterine growth restriction. Recently, the significance of the renin-angiotensin-aldosterone system (RAAS) that transfers from the donor to the recipient has attracted interest in the fetal circulation of TTTS. The donor has decreased renal blood flow due to decreased circulating blood volume. For this reason, the secretion of RAAS hormones is augmented in the fetal kidneys of the donor. In TTTS, these RAAS hormones from the donor transfer to the recipient through the anastomosed vessels. In addition to excess preload, the recipient heart is exposed to excess afterload due to systemic vasoconstriction through RAAS hormones. Commonly occurring complications in the recipient include myocardial hypertrophy, atrioventricular valve regurgitation, and pulmonary valve stenosis or pulmonary atresia. Fetoscopic laser photocoagulation (FLP) has been introduced recently because neither mortality nor neurological morbidity have been satisfactorily improved with conventional treatment. FLP is a curative method that may improve the prognosis of TTTS. In Japan, this procedure has been performed frequently, and positive neurological outcomes have been achieved.
Assuntos
Transfusão Feto-Fetal , Feto/irrigação sanguínea , Volume Sanguíneo , Cardiomegalia/embriologia , Cardiomegalia/etiologia , Feminino , Doenças Fetais/etiologia , Doenças Fetais/fisiopatologia , Retardo do Crescimento Fetal/etiologia , Transfusão Feto-Fetal/diagnóstico por imagem , Transfusão Feto-Fetal/etiologia , Transfusão Feto-Fetal/patologia , Transfusão Feto-Fetal/terapia , Fetoscopia , Humanos , Terapia com Luz de Baixa Intensidade , Poli-Hidrâmnios/etiologia , Gravidez , Prognóstico , Estenose da Valva Pulmonar/embriologia , Estenose da Valva Pulmonar/etiologia , Circulação Renal , Sistema Renina-Angiotensina/fisiologiaRESUMO
BACKGROUND: The expression of cardiac genes is precisely regulated, and any perturbation may cause developmental defects. In a previous study, we demonstrated that alcohol consumption during pregnancy could lead to uncontrolled expressions of cardiac genes and eventually result in cardiac dysplasia. However, the underlying mechanisms remain unclear. In the present study, we have investigated the alcohol-induced cardiac hypertrophy and its potential mechanisms. Furthermore, the protective effect of anacardic acid against the alcohol-induced cardiac hypertrophy has been explored in experimental mice. METHODS AND RESULTS: C57BL/6 pregnant mice were gavaged with 56% ethanol or saline and the hearts of their fetus were collected for analysis. Binding of p300, CBP, PCAF, SRC1, except GCN5, were increased to the NKX2.5 promoter in fetal mouse hearts exposed to alcohol. Increased acetylation of H3K9 and increased mRNA expression of NKX2.5, ß-MHC and Cx43 were observed in the same samples. Treatment with a pan-acetylase inhibitor, anacardic acid, reduced the binding affinity of p300 and PCAF to the NKX2.5, ß-MHC, Cx43 promoters and attenuated H3K9 hyperacetylation. Interestingly, anacardic acid down-regulated over-expression of these cardiac genes induced by alcohol and ultimately attenuated ethanol-induced cardiac hypertrophy in fetal mice. CONCLUSIONS: Our results indicate that alcohol exposure during pregnancy could lead to fetal cardiac hypertrophy. The over-expression of NKX2.5, ß-MHC, Cx43 mediated by p300 and PCAF may be critical mechanisms of alcohol-induced cardiac hypertrophy. Anacardic acid can down-regulate the over-expression of cardiac genes and reverse cardiac hypertrophy caused by alcohol treatment in pregnant mice, suggesting it could be a potential therapeutic agent for the treatment of cardiac hypertrophy.
Assuntos
Ácidos Anacárdicos/farmacologia , Cardiomegalia , Transtornos do Espectro Alcoólico Fetal , Histonas/metabolismo , Fatores de Transcrição de p300-CBP/metabolismo , Acetilação/efeitos dos fármacos , Animais , Cardiomegalia/embriologia , Cardiomegalia/patologia , Cardiomegalia/prevenção & controle , Etanol/toxicidade , Feminino , Transtornos do Espectro Alcoólico Fetal/metabolismo , Transtornos do Espectro Alcoólico Fetal/patologia , Transtornos do Espectro Alcoólico Fetal/prevenção & controle , Coração/embriologia , Camundongos , GravidezRESUMO
Global inactivation of the metalloproteinase ADAM17 during mouse development results in perinatal lethality and abnormalities of the heart, including late embryonic cardiomegaly and thickened semilunar and atrioventricular valves. These defects have been attributed in part to a lack of ADAM17-mediated processing of HB-EGF, as absence of soluble HB-EGF results in similar phenotypes. Because valvular mesenchymal cells are largely derived from cardiac endothelial cells, we generated mice with a floxed Adam17 allele and crossed these animals with Tie2-Cre transgenics to focus on the role of endothelial ADAM17 in valvulogenesis. We find that although hearts from late-stage embryos with ablation of endothelial ADAM17 appear normal, an increase in valve size and cell number is evident, but only in the semilunar cusps. Unlike Hbegf(-/-) valves, ADAM17-null semilunar valves do not differ from controls in acute cell proliferation at embryonic day 14.5 (E14.5), suggesting compensatory processing of HB-EGF. However, levels of the proteoglycan versican are significantly reduced in mutant hearts early in valve remodeling (E12.5). After birth, aortic valve cusps from mutants are not only hyperplastic but also show expansion of the glycosaminoglycan-rich component, with the majority of adults exhibiting aberrant compartmentalization of versican and increased deposition of collagen. The inability of mutant outflow valve precursors to transition into fully mature cusps is associated with decreased postnatal viability, progressive cardiomegaly, and systolic dysfunction. Together, our data indicate that ADAM17 is required in valvular endothelial cells for regulating cell content as well as extracellular matrix composition and organization in semilunar valve remodeling and homeostasis.
Assuntos
Proteínas ADAM/metabolismo , Envelhecimento/patologia , Células Endoteliais/enzimologia , Deleção de Genes , Valvas Cardíacas/patologia , Valvas Cardíacas/fisiopatologia , Proteína ADAM17 , Animais , Animais Recém-Nascidos , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/embriologia , Estenose da Valva Aórtica/patologia , Estenose da Valva Aórtica/fisiopatologia , Apoptose , Cardiomegalia/complicações , Cardiomegalia/embriologia , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Proliferação de Células , Colágeno/metabolismo , Cruzamentos Genéticos , Eletrocardiografia , Embrião de Mamíferos/anormalidades , Embrião de Mamíferos/patologia , Células Endoteliais/patologia , Matriz Extracelular/metabolismo , Feminino , Valvas Cardíacas/embriologia , Valvas Cardíacas/ultraestrutura , Fator de Crescimento Semelhante a EGF de Ligação à Heparina , Ácido Hialurônico/metabolismo , Integrases/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Camundongos , Receptor TIE-2/metabolismo , Análise de Sobrevida , Sístole , Versicanas/metabolismoRESUMO
Congenital tricuspid valve disease (Ebstein's anomaly, tricuspid valve dysplasia) with severe tricuspid regurgitation and cardiomegaly is associated with poor prognosis. Fetal echocardiography can accurately measure right atrial enlargement, which is associated with a poor prognosis in the fetus with tricuspid valve disease. Fetal lung volumetric assessments have been used in an attempt to predict viability of fetuses using ultrasonogram and prenatal MRI. We describe a fetus with tricuspid dysplasia, severe tricuspid regurgitation, right atrial enlargement and markedly reduced lung volumes. The early gestational onset of cardiomegaly with bilateral lung compression raised the possibility of severe lung hypoplasia with decreased broncho-alveolar development. Use of fetal echocardiography with measurement of pulmonary artery size combined with prenatal MRI scanning of lung volumes resulted in an improved understanding of this anomaly and directed the management strategy towards a successful Fontan circulation.
Assuntos
Anomalia de Ebstein/diagnóstico , Pulmão/embriologia , Diagnóstico Pré-Natal/métodos , Artéria Pulmonar/embriologia , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Valva Tricúspide/anormalidades , Adulto , Cardiomegalia/diagnóstico por imagem , Cardiomegalia/embriologia , Cardiomegalia/cirurgia , Ponte Cardiopulmonar , Anomalia de Ebstein/cirurgia , Feminino , Doenças Fetais/diagnóstico por imagem , Idade Gestacional , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/cirurgia , Humanos , Recém-Nascido , Pulmão/diagnóstico por imagem , Imageamento por Ressonância Magnética , Gravidez , Artéria Pulmonar/cirurgia , Valva Tricúspide/embriologia , Valva Tricúspide/cirurgia , Insuficiência da Valva Tricúspide/cirurgia , Ultrassonografia Pré-NatalRESUMO
OBJECTIVES: To describe our experience in cases with sonographic signs of fetal infection and with maternal serological 'immunity' to cytomegalovirus (CMV) infection. METHODS: This was a bicenter study of six pregnant women referred for evaluation of suspected fetal infection. All cases had confirmed maternal serology for past exposure to CMV but no evidence of recent secondary CMV infection. All underwent sonographic evaluation as well as complete investigation for CMV infection. RESULTS: The mean age of the women was 29 (range, 23-35) years and the mean gestational age at diagnosis was 23.5 weeks (range, 20-31) weeks. Sonographic findings included microcephaly, ventriculomegaly, periventricular calcifications and cystic lesions, echogenic bowel, hydrops and hepatosplenomegaly. Amniocentesis was performed in all cases for fetal karyotyping and viral assessment, and all were found by polymerase chain reaction to be positive for CMV infection. Four pregnancies were terminated following the parents' request. One pregnancy continued until intrauterine fetal death occurred 2 weeks after diagnosis. Postmortem was denied in all cases but one. One infant was delivered with evidence of severe cerebral palsy. CONCLUSION: In the presence of sonographic findings suggestive of fetal CMV infection, prompt investigation of amniotic fluid should follow even if maternal serology does not support recent maternal seroconversion.
Assuntos
Infecções por Citomegalovirus/transmissão , Citomegalovirus , Doenças Fetais/virologia , Complicações Infecciosas na Gravidez/imunologia , Adulto , Amniocentese , Líquido Amniótico/virologia , Anticorpos Antivirais/sangue , Cardiomegalia/diagnóstico por imagem , Cardiomegalia/embriologia , Cardiomegalia/virologia , Paralisia Cerebral/diagnóstico por imagem , Paralisia Cerebral/embriologia , Paralisia Cerebral/virologia , Citomegalovirus/genética , Infecções por Citomegalovirus/embriologia , DNA Viral/análise , Feminino , Retardo do Crescimento Fetal/diagnóstico por imagem , Retardo do Crescimento Fetal/virologia , Humanos , Imunoglobulina G/sangue , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Enteropatias/diagnóstico por imagem , Enteropatias/embriologia , Enteropatias/virologia , Hepatopatias/diagnóstico por imagem , Hepatopatias/embriologia , Hepatopatias/virologia , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Ultrassonografia Pré-Natal/métodos , Carga ViralRESUMO
We report the case of a young primigravida who presented with a 20 weeks pregnancy with a previous diagnosis of uterine fibroid. However, ultrasound evaluation revealed the presence of a large sacro-coccygeal teratoma in the foetus which was heterogeneous with cystic areas and calcific foci, and showed increased vascularity. There was also evidence of foetal cardiomegaly and hydrops foetalis, indicated by subcutaneous oedema in the foetus,thickened placenta and polyhydramnios. The presence of hydrops with sacro-coccygeal teratoma has a grave prognosis for the mother and child; hence termination of pregnancy was done. A 20 weeks old foetus with a huge sacro-coccygeal mass, which was ruptured at many places and showed areas of active bleed, was expelled.
Assuntos
Anormalidades Múltiplas/diagnóstico por imagem , Cardiomegalia/diagnóstico por imagem , Hidropisia Fetal/diagnóstico por imagem , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Teratoma/diagnóstico por imagem , Anormalidades Múltiplas/embriologia , Aborto Eugênico , Adulto , Cardiomegalia/embriologia , Evolução Fatal , Feminino , Humanos , Gravidez , Resultado da Gravidez , Segundo Trimestre da Gravidez , Região Sacrococcígea , Neoplasias da Coluna Vertebral/embriologia , Teratoma/embriologia , Ultrassonografia Pré-Natal , Adulto JovemRESUMO
In the adult heart, a variety of stresses induce re-expression of a fetal gene program in association with myocyte hypertrophy and heart failure. Here we show that histone deacetylase-2 (Hdac2) regulates expression of many fetal cardiac isoforms. Hdac2 deficiency or chemical histone deacetylase (HDAC) inhibition prevented the re-expression of fetal genes and attenuated cardiac hypertrophy in hearts exposed to hypertrophic stimuli. Resistance to hypertrophy was associated with increased expression of the gene encoding inositol polyphosphate-5-phosphatase f (Inpp5f) resulting in constitutive activation of glycogen synthase kinase 3beta (Gsk3beta) via inactivation of thymoma viral proto-oncogene (Akt) and 3-phosphoinositide-dependent protein kinase-1 (Pdk1). In contrast, Hdac2 transgenic mice had augmented hypertrophy associated with inactivated Gsk3beta. Chemical inhibition of activated Gsk3beta allowed Hdac2-deficient adults to become sensitive to hypertrophic stimulation. These results suggest that Hdac2 is an important molecular target of HDAC inhibitors in the heart and that Hdac2 and Gsk3beta are components of a regulatory pathway providing an attractive therapeutic target for the treatment of cardiac hypertrophy and heart failure.
Assuntos
Cardiomegalia/enzimologia , Quinase 3 da Glicogênio Sintase/metabolismo , Histona Desacetilases/fisiologia , Proteínas Repressoras/fisiologia , Animais , Cardiomegalia/embriologia , Cardiomegalia/genética , Ativação Enzimática/fisiologia , Feto , Glicogênio Sintase Quinase 3 beta , Histona Desacetilase 2 , Histona Desacetilases/biossíntese , Histona Desacetilases/deficiência , Histona Desacetilases/genética , Isoenzimas/metabolismo , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Dados de Sequência Molecular , Proteínas Repressoras/biossíntese , Proteínas Repressoras/genética , Transdução de Sinais/fisiologiaRESUMO
OBJECTIVES: We investigated the impact of selective laser ablation on the cardiovascular pathology of the recipient twin in twin-twin transfusion syndrome. STUDY DESIGN: Fetal echocardiograms and medical records were reviewed from 22 pregnancies with severe twin-twin transfusion syndrome where echocardiography was performed before and after laser. RESULTS: Before laser, cardiomegaly associated with right and/or left ventricular hypertrophy without ventricular dilatation, was observed in most cases. Right ventricular and left ventricular systolic dysfunction (shortening fraction <28%) was present in 59% and 27%, respectively, and diastolic dysfunction (based on inflow and venous Dopplers) in 73%. Shortly after laser, biventricular systolic function improved significantly and diastolic function tended to improve (50%, P = .06). Functional pulmonary atresia, secondary to right ventricular systolic dysfunction, resolved in 2 of 2 cases at post-laser echocardiography. On serial assessment, diastolic function was normal in 7 of 10, hydrops regressed in 4 of 5, and neither progressive myocardial hypertrophy nor anatomical right ventricular outflow obstruction were found. CONCLUSIONS: Selective laser ablation in severe twin-twin transfusion syndrome acutely improves biventricular systolic function and tends to improve diastolic function in the recipient twin.
Assuntos
Anastomose Arteriovenosa/cirurgia , Cardiomegalia/embriologia , Transfusão Feto-Fetal/cirurgia , Cardiopatias/embriologia , Terapia a Laser , Placenta/irrigação sanguínea , Gêmeos , Adulto , Cardiomegalia/diagnóstico por imagem , Ecocardiografia , Feminino , Transfusão Feto-Fetal/diagnóstico por imagem , Transfusão Feto-Fetal/fisiopatologia , Cardiopatias/fisiopatologia , Humanos , Hidropisia Fetal/fisiopatologia , Gravidez , Índice de Gravidade de Doença , Função VentricularRESUMO
Organ size is precisely regulated during development, but the control mechanisms remain obscure. We have isolated a mutation in zebrafish, liebeskummer (lik), which causes development of hyperplastic embryonic hearts. lik encodes Reptin, a component of a DNA-stimulated ATPase complex. The mutation activates ATPase activity of Reptin complexes and causes a cell-autonomous proliferation of cardiomyocytes to begin well after progenitors have fashioned the primitive heart tube. With regard to heart growth, beta-catenin and Pontin, a DNA-stimulated ATPase that is often part of complexes with Reptin, are in the same genetic pathways. Pontin reduction phenocopies the cardiac hyperplasia of the lik mutation. Thus, the Reptin/Pontin ratio serves to regulate heart growth during development, at least in part via the beta-catenin pathway.
Assuntos
Coração/embriologia , Proteínas Nucleares/fisiologia , Proteínas de Peixe-Zebra/fisiologia , Proteases Dependentes de ATP , Adenosina Trifosfatases/química , Adenosina Trifosfatases/fisiologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Cardiomegalia/embriologia , Cardiomegalia/etiologia , Cardiomegalia/genética , Proteínas de Transporte , Divisão Celular , Sequência Conservada , Proteínas do Citoesqueleto/fisiologia , Embrião não Mamífero , Ativação Enzimática , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Choque Térmico/fisiologia , Dados de Sequência Molecular , Miocárdio/citologia , Miocárdio/ultraestrutura , Proteínas Nucleares/genética , Mutação Puntual , Homologia de Sequência de Aminoácidos , Serina Endopeptidases/fisiologia , Transativadores/fisiologia , Peixe-Zebra , Proteínas de Peixe-Zebra/química , Proteínas de Peixe-Zebra/genética , beta CateninaAssuntos
Cardiomegalia/diagnóstico por imagem , Doenças Fetais/diagnóstico por imagem , Hemangioma/diagnóstico por imagem , Doenças Placentárias/diagnóstico por imagem , Adulto , Cardiomegalia/embriologia , Cardiomegalia/patologia , Feminino , Doenças Fetais/patologia , Idade Gestacional , Hemangioma/patologia , Humanos , Recém-Nascido , Doenças Placentárias/patologia , Gravidez , Síndrome do Desconforto Respiratório do Recém-Nascido/patologia , Ultrassonografia Pré-NatalRESUMO
In cardiac muscle, the selectivity and specificity of gene regulation by heparin-binding and transforming growth factors resembles the characteristic program of fetal gene induction during myocardial hypertrophy produced by load. Shared by isolated cardiac myocytes and intact hearts, these complex and heterogeneous responses provide intriguing systems, which are distinct from other lineages and models of cell growth, for the study of trophic signal transduction by cellular oncogenes. A functional role for peptide growth factors and other oncogene-encoded proteins in myocardial hypertrophy suggests biological pathways which might usefully be exploited to promote compensatory growth following infarction or to interfere with maladaptive changes during a hemodynamic load.
Assuntos
Substâncias de Crescimento/fisiologia , Coração/fisiologia , Proteínas Oncogênicas/fisiologia , Transdução de Sinais/fisiologia , Estresse Mecânico , Actinas/fisiologia , Animais , Cardiomegalia/embriologia , Cardiomegalia/genética , Cardiomegalia/patologia , Regulação da Expressão Gênica/fisiologia , Substâncias de Crescimento/genética , Humanos , Proteínas Oncogênicas/genética , Transdução de Sinais/genética , Ativação TranscricionalAssuntos
Cardiomiopatias , Adolescente , Adulto , Cardiomegalia/diagnóstico , Cardiomegalia/embriologia , Cardiomegalia/patologia , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/patologia , Criança , Pré-Escolar , Morte Súbita/etiologia , Fibroelastose Endocárdica/patologia , Feminino , Doença de Depósito de Glicogênio/patologia , Neoplasias Cardíacas , Ventrículos do Coração/patologia , Humanos , Lactente , Recém-Nascido , Masculino , Miocardite/patologia , Miocárdio/patologiaRESUMO
Triac (diethanolamine salt of triiodothyroacetic acid) was administered by intramuscular injection to 12 pregnant female rats. These were divided into a control group and three other groups, each receiving different doses of triac. The effect of triac on the hearts of their offspring was studied morphologically. Histological examination showed evidence of only mild hypertrophy, but ultrastructurally, disarray of myocardial fibrils and other changes similar to those observed in patients with hypertrophic cardiomyopathy were found in the litter of the group receiving the highest dose. It is suggested that thyroid function should be studied in patients with obscure cardiac disease.