RESUMO
Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiomyopathy and is characterized by increased left ventricular wall thickness, but existing diagnostic and treatment approaches face limitations. MicroRNAs (miRNAs) are type of noncoding RNA molecule that plays crucial roles in the pathological process of cardiac remodelling. Accordingly, miRNAs related to HCM may represent potential novel therapeutic targets. In this review, we first discuss the different roles of miRNAs in the development of HCM. We then summarize the roles of common miRNAs as diagnostic and clinical biomarkers in HCM. Finally, we outline current and future challenges and potential new directions for miRNA-based therapeutics for HCM.
Assuntos
Cardiomiopatia Hipertrófica , MicroRNAs , Biomarcadores , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/terapia , Humanos , MicroRNAs/genéticaRESUMO
BACKGROUND: Primary cardiac tumors are rare in all age groups and are usually benign. Symptoms are usually related to tumor size, location, invasiveness, number, and growth rate. While histologically benign, cardiac arrest may be caused by blocked inflow or outflow or malignant ventricular arrhythmia. Surgical resection of left ventricular tumors, especially those involving the outflow tract, is challenging. CASE PRESENTATION: Herein, we present a rare case of an asymptomatic, 39-year-old woman who was referred to our cardiovascular department for a huge left ventricular cardiac mass incidentally discovered during the physical examination. Images showed a huge mass that quasi-circular low-density focus with a clear boundary and regular shape in the left ventricular cavity and fortunately had no significant effect on the peripheral valves and hemodynamics. CONCLUSIONS: This illustrative report highlights the exact surgical management of a cardiac tumor depends largely on the site and extent of the mass. Mechanical compromise and not the neoplastic potential should be considered. A conservative approach and follow-up regularly are advocated to ensure that the patient gets the best diagnosis and treatment, however, surgery is indicated only for severely symptomatic patients with hemodynamic compromise.
Assuntos
Parada Cardíaca , Neoplasias Cardíacas , Lipoma , Adulto , Feminino , Neoplasias Cardíacas/complicações , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/cirurgia , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Ventrículos do Coração/cirurgia , Hemodinâmica , Humanos , Lipoma/complicações , Lipoma/diagnóstico por imagem , Lipoma/cirurgiaRESUMO
BACKGROUND: Although most cases of atrial septal defect (ASD) are sporadic, familial cases have been reported, which may be caused by mutation of transcription factor GATA binding protein 4 (GATA4). Herein we combined whole-exome sequencing and bioinformatics strategies to identify a novel mutation in GATA4 accounting for the etiology in a Chinese family with ASD. METHODS: We identified kindred spanning 3 generations in which 3 of 12 (25.0%) individuals had ASD. Punctilious records for the subjects included complete physical examination, transthoracic echocardiography, electrocardiograph and surgical confirming. Whole-exome capture and high-throughput sequencing were performed on the proband III.1. Sanger sequencing was used to validate the candidate variants, and segregation analyses were performed in the family members. RESULTS: Direct sequencing of GATA4 from the genomic DNA of family members identified a T-to-C transition at nucleotide 929 in exon 5 that predicted a methionine to threonine substitution at codon 310 (M310T) in the nuclear localization signal (NLS) region. Two affected members (II.2 and III.3) and the proband (III.1) who was recognized as a carrier exhibited this mutation, whereas the other unaffected family members or control individuals did not. More importantly, the mutation GATA4 (c.T929C: p.M310T) has not been reported previously in either familial or sporadic cases of congenital heart defects (CHD). CONCLUSIONS: We identified for the first time a novel M310T mutation in the GATA4 gene that is located in the NLS region and leads to family ASD with arrhythmias. However, the mechanism by which this pathogenic mutation contributes to the development of heart defect and tachyarrhythmias remains to be ascertained.
Assuntos
Arritmias Cardíacas/genética , Fator de Transcrição GATA4/genética , Comunicação Interatrial/genética , Mutação , Adolescente , Adulto , Idoso , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatologia , Criança , Pré-Escolar , Biologia Computacional , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Comunicação Interatrial/diagnóstico , Comunicação Interatrial/fisiopatologia , Hereditariedade , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Sequenciamento do ExomaRESUMO
BACKGROUND: Early identification of congenital heart disease (CHD) allows detection of the pulmonary arteriopathy in an early stage, and timely shunt closure can permanently reverse pulmonary arterial hypertension (PAH). However, surgical correction is not recommended in patients with irreversible PAH. Herein we report our experience about Eisenmenger's syndrome in simple CHD. CASE PRESENTATION: From January 2017 to November 2018, a total of 8 CHD patients (3 ventricular septal defects (VSD), 2 atrial septal defects (ASD), and 3 patent ductus arteriosus (PDA), median age, 15.5 years [range, 3-18 years]) with PAH were detected by chest X-ray, electrocardiogram, transthoracic echocardiography (TTE), computed tomographic angiography (CTA) and cardiac catheterization. The median defect diameter, pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR) were 16.5 mm (range, 3-30 mm), 75 mmHg (range, 60-86 mmHg), and 16 Woods units (range, 12-19 Woods units), respectively. Here, we report the representative cases of three types of simple CHD with irreversible PAH. The surgical correction was not performed in all patients who had fixed PAH and were referred to medical treatment. CONCLUSIONS: PAH in CHD can be reversed by early shunt closure, but this potential is lost beyond a certain point of no return. This article highlights the essence of enhancing the level of healthcare and services in Chinese rural areas. Failure to accurately and timely assess PAH will delay effective treatment past optimal treatment time, and even lead to death.
Assuntos
Angiografia por Tomografia Computadorizada , Ecocardiografia , Complexo de Eisenmenger/diagnóstico por imagem , Hipertensão Arterial Pulmonar/etiologia , Artéria Pulmonar/diagnóstico por imagem , Adolescente , Pressão Arterial , Criança , Diagnóstico Precoce , Complexo de Eisenmenger/complicações , Complexo de Eisenmenger/fisiopatologia , Complexo de Eisenmenger/terapia , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Prognóstico , Hipertensão Arterial Pulmonar/diagnóstico por imagem , Hipertensão Arterial Pulmonar/fisiopatologia , Hipertensão Arterial Pulmonar/terapia , Artéria Pulmonar/fisiopatologiaRESUMO
BACKGROUND: Traditional percutaneous device closure of perimembranous ventricular septal defects (PmVSDs) is a minimally invasive technique, but can result in high radiation exposure and can result in potential arterial complications. Here, we aimed to assess the safety and feasibility of device closure of PmVSDs via the femoral vein approach under transesophageal echocardiography (TEE) guidance in children. METHODS: From January 2014 to December 2017, a total of 46 PmVSD patients (mean age, 6.5 ± 2.3 years [range, 4.2-12.0 years]; mean body weight 22.1 ± 6.6 kg [range, 16.0-38.5 kg]; VSD diameter, 4.1 ± 0.6 mm [range, 3.2-5.0 mm]) underwent attempted transcatheter closure via the femoral vein approach under the guidance of TEE without fluoroscopy. RESULTS: The transcatheter occlusion procedure under TEE guidance was successful in 44 (95.7%) patients. Surgery was necessary in 2 (4.3%) patients. The procedure duration was 28.2 ± 8.7 min (range, 12.0-42.0 min). One patient had immediate post-operative trivial residual shunt and three patients had immediate incomplete right bundle branch block (IRBBB) after operation; the new IRBBB in 1 case was noted in the first postoperative month. No residual shunt was noted at 3 months after the procedure, and no intervention related complications were detected at 1-24 months follow-up. CONCLUSIONS: Percutaneous device closure of PmVSDs under TEE guidance solely by femoral vein approach is effective and safe, avoids radiation exposure, potential arterial complications and a surgical incision.
Assuntos
Ecocardiografia Transesofagiana , Comunicação Interventricular/terapia , Dispositivo para Oclusão Septal , Cateterismo Cardíaco/métodos , Criança , Pré-Escolar , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Veia Femoral , Comunicação Interventricular/diagnóstico por imagem , Humanos , Masculino , Ilustração Médica , Duração da Cirurgia , Exposição à Radiação/prevenção & controleRESUMO
OBJECTIVE: To explore the effects of KIAA0196 gene on cardiac development and the establishment of zebrafish strain.â© Methods: Peripheral blood and gDNA from patients were extracted. Copy number variation analysis and target sequencing were conducted to screen candidate genes. The KIAA0196 knockout zebraï¬sh was generated by CRISPR/Cas9 to detect whether KIAA0196 deï¬ciency could affect cardiac development. Finally, the wild-type and mutant zebrafish were anatomized and histologically stained to observe the phenotype of heart defects.â© Results: The KIAA0196 knockout zebrafish strain was successfully constructed using CRISPR/Cas9 technology. After 60 hours fertilization, microscopic examination of KIAA0196 knockout zebrafish (heterozygote + homozygote) showed pericardial effusion, cardiac compression and severely curly tail. Compared with wild-type zebrafish, the hearts of mutant KIAA0196 zebraï¬sh had cardiac defects including smaller atrium and larger ventricle, and the myocardial cells were looser.â© Conclusion: KIAA0196 gene plays an important regulatory role in the development of heart. It might be a candidate gene for congenital heart disease.
Assuntos
Cardiopatias Congênitas/genética , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/genética , Animais , Variações do Número de Cópias de DNA , Coração , Humanos , Miócitos Cardíacos , Fenótipo , ProteínasRESUMO
BACKGROUND: Congenital heart disease (CHD), plus cleft lip and palate (CLP) are currently the most common types of structural malformation in infants. Many genes have been investigated for their involvement in CHD with CLP. Targeted next-generation sequencing can analyze large amounts of genetic information rapidly, and thus address this question. METHODS: The authors designed a targeted, next-generation sequencing gene panel for 455 genes previously implicated in CHD or CLP. A single-subject patient served as a genetic source. Variants that affect protein-coding regions were classified into silico and filtered through databases, such as the Single-Nucleotide Polymorphism Database, Yan Huang, the Exome Sequencing Project, and the 1000 Genomes Project. The authors then predicted the function of gene mutations by PolyPhen-2, SIFT, and Mutation Taster. To confirm the related disease genes, the authors surveyed relevant literature on PubMed. Finally, the variant was verified by Sanger sequencing. RESULTS: A total of 1520 mutations were successfully found in a patient using combined tetralogy of Fallot and CLP by the targeted next-generation sequencing. However, there were 6 gene mutations (ZNF528, PVRL2, methylenetetrahydrofolate reductase [MTHFR], EVC2, DAND5, CCDC39) that were not found on Single-Nucleotide Polymorphism Database, Yan Huang, Exome Sequencing Project, and 1000 Genomes Project. Four genes (ZNF528, PVRL2, EVC2, CCDC39) were all predicted to be "tolerated," "benign," or "polymorphic" by SIFT, PolyPhen-2, and Mutation Taster. The DAND5 gene was predicted to be "possibly damaging" and "disease causing" respectively by PolyPhen-2 and Mutation Taster, but the SIFT program predicted this mutation to be "tolerated." Likewise, the MTHFR gene mutation was predicted to be "damaging," "possibly damaging," and "disease causing" respectively by SIFT, PolyPhen-2, and Mutation Taster. There is no relevant report about MTHFR gene mutation (c.G586A, p.G196S) on PubMed. CONCLUSION: Using targeted, next-generation sequencing technology, the authors identified for the first time a mutation (c.G586A, p.G196S) in the MTHFR gene as a possible cause of TOF and CLP in a patient.
Assuntos
Fenda Labial/genética , Fissura Palatina/genética , Mutação/genética , Tetralogia de Fallot/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , LactenteRESUMO
OBJECTIVE: To investigate the feasibility and safety of perimembranous ventricular septal defects (PmVSD) closure solely by femoral vein approach under transesophageal echocardiography (TEE) guidance.â© Methods: From January 1, 2014 to May 31, 2016, 26 patients with PmVSD in Second Xiangya Hospital were selected, with age at 3.2-6.0 (4.3±0.7) years old and body weight at 15.0-19.5 (16.7±1.4) kg. The diameter of VSD was 3.5-4.8 (4.1±0.3) mm. All patients were treated by percutaneous PmVSD closure solely by femoral vein approach under TEE guidance. The effect of the procedure was evaluated by TEE and transthoracic echocardiography (TTE). The clinical follow-up study was conducted by TTE at 1, 3, 6 and 12 month (s) after the procedure.â© Results: Twenty cases were successfully treated with percutaneous PmVSD closure solely by femoral vein approach under TEE guidance, and the success rate was 76.9%. Six patients were converted to perventricular closure under TEE guidance because the guide wire in two cases or catheter in other cases could not pass through PmVSD. The diameter of symmetrical VSD occluder was 6.0-7.0 (6.2±0.4) mm. The procedural time was 12.0-64.0 (26.8±6.3) min. The residence time at ICU was 1.8-2.4 (26.8±6.3) h. The in-hospital time was 4.0-5.0 (4.4±0.5) d. There were 3 patients with immediate post-operative trivial residual shunt and incomplete right bundle branch block (IRBBB). All patients survived with no peripheral vascular injury or complications such as tricuspid regurgitation, pericardial tamponade and pulmonary infection. The residual shunt disappeared in 3 patients and IRBBB became normal rhythm in 3 patients at 1 month follow-up time point. No patients suffered from occluder malposition, residual shunt, pericardial effusion, arrhythmia (atrio-ventricular block), aortic valve regurgitation and tricuspid regurgitation.â© Conclusion: TEE-guided percutaneous PmVSD closureby femoral vein approach is safe and effective.
Assuntos
Ecocardiografia Transesofagiana , Comunicação Interventricular/cirurgia , Criança , Pré-Escolar , Veia Femoral , Seguimentos , Humanos , Dispositivo para Oclusão Septal , Resultado do TratamentoAssuntos
Aorta Torácica/anormalidades , Cianose/etiologia , Permeabilidade do Canal Arterial/complicações , Malformações Vasculares/complicações , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/fisiopatologia , Aortografia , Criança , Angiografia por Tomografia Computadorizada , Cianose/fisiopatologia , Permeabilidade do Canal Arterial/diagnóstico por imagem , Permeabilidade do Canal Arterial/fisiopatologia , Humanos , Masculino , Malformações Vasculares/diagnóstico por imagem , Malformações Vasculares/fisiopatologiaRESUMO
Congenital heart disease (CHD), birth defect with the highest incidence rates worldwide, and is mainly characterized by the abnormal internal structure of the heart or/and the anatomical structure of great vessels. In the past few decades, CHD repair surgery through standard median sternotomy incision combined with cardiopulmonary bypass (CPB) technology has been considered the gold standard for surgical correction of heart and great vessels. With the promotion and clinical application of interventional catheterization technology, transcatheter closure of CHD under radioactive radiation has gradually been recognized and applied. However, its radiation exposure and potential complications related to arteriovenous vessels still face challenges. In recent years, an increasing number of surgeons have explored new surgical procedures, for the safe and effective treatment of CHD, as far as possible to reduce surgical trauma, avoid radiation exposure, and improve the cosmetic effect. Therefore, on the premise of satisfactory exposure or guidance, how to integrate ultrasound and percutaneous interventional technology remained the focus of the exploration. This mini-review highlights and summarizes the signs of progress of ultrasound intervention in the last decade that have proven the effectiveness and operability of a well-established procedure for percutaneous closure of congenital heart diseases under echocardiographic guidance only. We discuss potential diseases that will benefit from this emerging procedure based on this progress. Owing to the crucial advantages played by this strategy in the treatment of CHD, better understanding and promotion of this less exploited field may contribute to the development of therapeutics targeting CHD, improve medical utilization rate, promote the optimization of medical resources, and ultimately achieve precise and efficient medical treatment.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Cardiopatias Congênitas , Comunicação Interatrial , Humanos , Ecocardiografia Transesofagiana , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/cirurgia , Ecocardiografia , Resultado do Tratamento , Cateterismo Cardíaco/métodos , Comunicação Interatrial/cirurgiaRESUMO
Modifier genes contribute significantly to our understanding of pathophysiology in human diseases; however, effective approaches to identify modifier genes are still lacking. Here, we aim to develop a rapid F0-based genetic assay in adult zebrafish using the bag3 gene knockout (bag3e2/e2) cardiomyopathy model as a paradigm. First, by utilizing a classic genetic breeding approach, we identified dnajb6b as a deleterious modifier gene for bag3 cardiomyopathy. Next, we established an F0-based genetic assay in adult zebrafish through injection of predicted microhomology-mediated end joining (MMEJ)-inducing single guide RNA/Cas9 protein complex. We showed that effective gene knockdown is maintained in F0 adult fish, enabling recapitulation of both salutary modifying effects of the mtor haploinsufficiency and deleterious modifying effects of the dnajb6b gene on bag3 cardiomyopathy. We finally deployed the F0-based genetic assay to screen differentially expressed genes in the bag3 cardiomyopathy model. As a result, myh9b was identified as a novel modifier gene for bag3 cardiomyopathy. Together, these data prove the feasibility of an F0 adult zebrafish-based genetic assay that can be effectively used to discover modifier genes for inherited cardiomyopathy.
Assuntos
Cardiomiopatias , Peixe-Zebra , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Proteínas Reguladoras de Apoptose/genética , Cardiomiopatias/genética , Técnicas de Inativação de Genes , Genes Modificadores , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , RNA Guia de Sistemas CRISPR-CasRESUMO
The aortic anomaly of the right coronary artery (AAORCA) originating from the left aortic sinus (LCS) is a rare malformation that may result in sudden cardiac death (SCD), which may be due to the dilated aorta-pulmonary artery affecting the blood supply of the coronary artery. However, there are still some disputes about the treatment of the AAORCA. Herein, we present a rare case of AAORCA from the LCS with aortic dissection (AD). Considering the risk of dissection rupture and SCD, an emergency surgery of aortic replacement and coronary anomaly correction was performed successfully for the patient. This report illustrated that AAORCA complicated with acute AD (AAD) is lethal and may promote the occurrence of coronary ischemia or sudden death by a new "double-kill" mechanism that myocardial ischemia was based on the extent of a fixed and a dynamic component like slit-like ostium, proximal narrowing, acute take-off angle and intramural course with the elliptic vessel shape. There is no doubt that surgery is the best treatment option for the AAORCA with AAD.
RESUMO
Previously we showed the generation of a protein trap library made with the gene-break transposon (GBT) in zebrafish (Danio rerio) that could be used to facilitate novel functional genome annotation towards understanding molecular underpinnings of human diseases (Ichino et al, 2020). Here, we report a significant application of this library for discovering essential genes for heart rhythm disorders such as sick sinus syndrome (SSS). SSS is a group of heart rhythm disorders caused by malfunction of the sinus node, the heart's primary pacemaker. Partially owing to its aging-associated phenotypic manifestation and low expressivity, molecular mechanisms of SSS remain difficult to decipher. From 609 GBT lines screened, we generated a collection of 35 zebrafish insertional cardiac (ZIC) mutants in which each mutant traps a gene with cardiac expression. We further employed electrocardiographic measurements to screen these 35 ZIC lines and identified three GBT mutants with SSS-like phenotypes. More detailed functional studies on one of the arrhythmogenic mutants, GBT411, in both zebrafish and mouse models unveiled Dnajb6 as a novel SSS causative gene with a unique expression pattern within the subpopulation of sinus node pacemaker cells that partially overlaps with the expression of hyperpolarization activated cyclic nucleotide gated channel 4 (HCN4), supporting heterogeneity of the cardiac pacemaker cells.
Assuntos
Síndrome do Nó Sinusal , Peixe-Zebra , Camundongos , Animais , Humanos , Síndrome do Nó Sinusal/genética , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Nó Sinoatrial/metabolismo , Fenótipo , Eletrocardiografia/efeitos adversos , Arritmias Cardíacas/metabolismo , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Chaperonas Moleculares/metabolismo , Proteínas de Choque Térmico HSP40/genéticaRESUMO
An anomalous left hepatic venous (LHV) connection is an extremely rare cardiac malformation, and left hepatic venous route abnormalities not associated with other cardiac lesions do not require surgical treatment because they are physiologically benign. However, when venous route abnormalities exist with associated cardiac lesions, the conduct of the cardiac surgical repair must accommodate the abnormal venous anatomy, especially in total cavopulmonary connection patients. Herein, we present a rare case of a 7-year-old Chinese boy about 1 year post bilateral superior vena cava pulmonary anastomosis who presented with severe cyanosis and was referred to our department. However, the patient showed an unexpected gradual decrease in blood oxygen saturation to 60-70% after the extracardiac total cavopulmonary connection (ETCPC) operation. Emergency echocardiography and computed tomography confirmed that the LHV entered the right atrium. Subsequently, the patient undergone completion of a staged TCPC with intra-atrial tunnel technique. This illustrative report highlights the essence of improving the preoperative accurate diagnosis to avoid unplanned reoperation in China, especially for the remote rural areas of eastern countries where the level of health care and services is relatively backward. Failure to identify anomalous LHV connection, in this case, will delay effective treatment past the optimal treatment time.
RESUMO
OBJECTIVES: The feasibility of mini-invasive closure of perimembranous ventricular septal defects has been proven, but can cause surgical incision or sternum injury. A relevant but, to date, unanswered question is whether there exists a treatment without surgical trauma, radiation exposure and arterial complications. METHODS: From May 2017 to January 2020, a total of 449 patients with perimembranous ventricular septal defect [mean age 5.0 ± 6.1 years (range 0.8-52.0 years)] were involved in this study and underwent 2 different echocardiography-guided operative procedures [percutaneous device closure (group A) or percardiac device closure (group B)] based on the patients' or their parents' choice. The clinical data were collected and a retrospective analysis was performed. RESULTS: Fifty-five (96.5%) cases were successfully occluded in group A, and 2 (3.5%) patients were converted to percardiac device closure; 379 (96.7%) patients in group B underwent percardiac device closure, and 13 patients (3.3%) were turned to open-heart surgery after occlusion procedure failure. There were statistically significant differences (P < 0.05) between the 2 groups in operation time, postoperative hospitalization time and blood transfusion requirement. No acute complications or severe adverse events (death, valve injury, complete atrioventricular block and embolism) occurred either in the early period or during the follow-up. CONCLUSIONS: Percutaneous device closure can achieve the same validity and safety as percardiac device closure for treating perimembranous ventricular septal defects with a more rapid recovery and less trauma.
Assuntos
Comunicação Interventricular , Dispositivo para Oclusão Septal , Adolescente , Adulto , Cateterismo Cardíaco , Criança , Pré-Escolar , Ecocardiografia , Ecocardiografia Transesofagiana , Seguimentos , Humanos , Lactente , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Myosin heavy chain 7 (MYH7) is a major causative gene for hypertrophic cardiomyopathy, but the affected signaling pathways and therapeutics remain elusive. In this research, we identified ventricle myosin heavy chain like (vmhcl) as a zebrafish homolog of human MYH7, and we generated vmhcl frameshift mutants. We noted vmhcl-based embryonic cardiac dysfunction (VEC) in the vmhcl homozygous mutants and vmhcl-based adult cardiomyopathy (VAC) phenotypes in the vmhcl heterozygous mutants. Using the VEC model, we assessed 7 known cardiomyopathy signaling pathways pharmacologically and 11 candidate genes genetically via CRISPR/Cas9 genome editing technology based on microhomology-mediated end joining (MMEJ). Both studies converged on therapeutic benefits of mTOR or mitogen-activated protein kinase (MAPK) inhibition of VEC. While mTOR inhibition rescued the enlarged nuclear size of cardiomyocytes, MAPK inhibition restored the prolonged cell shape in the VEC model. The therapeutic effects of mTOR and MAPK inhibition were later validated in the VAC model. Together, vmhcl/myh7 loss of function is sufficient to induce cardiomyopathy in zebrafish. The VEC and VAC models in zebrafish are amenable to both efficient genetic and chemical genetic tools, offering a rapid in vivo platform for discovering candidate signaling pathways of MYH7 cardiomyopathy.
Assuntos
Cardiomiopatias/terapia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Animais , Modelos Animais de Doenças , Peixe-ZebraRESUMO
Zebrafish is a powerful and widely-used model system for a host of biological investigations, including cardiovascular studies and genetic screening. Zebrafish are readily assessable during developmental stages; however, the current methods for quantifying and monitoring cardiac functions mainly involve tedious manual work and inconsistent estimations. In this paper, we developed and validated a Zebrafish Automatic Cardiovascular Assessment Framework (ZACAF) based on a U-net deep learning model for automated assessment of cardiovascular indices, such as ejection fraction (EF) and fractional shortening (FS) from microscopic videos of wildtype and cardiomyopathy mutant zebrafish embryos. Our approach yielded favorable performance with accuracy above 90% compared with manual processing. We used only black and white regular microscopic recordings with frame rates of 5-20 frames per second (fps); thus, the framework could be widely applicable with any laboratory resources and infrastructure. Most importantly, the automatic feature holds promise to enable efficient, consistent, and reliable processing and analysis capacity for large amounts of videos, which can be generated by diverse collaborating teams.
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Cardiomiopatias , Sistema Cardiovascular , Aprendizado Profundo , Animais , Contração Miocárdica , Peixe-ZebraRESUMO
A redo surgical approach to residual ventricular septal defect (VSD) is technically demanding. Sternum reentry has to be performed very carefully to avoid any uncontrolled bleeding, and preparation of the adhesions must be made to expose the most important structures (ascending aorta, caval veins). However, percutaneous transcatheter device closure of the residual VSD with radiation exposure can cause arrhythmia, valve injury, and vascular complications. This report presents a less invasive technique to treat residual VSD, without arterial access, radiation exposure, or cardiopulmonary bypass.