Clinical Implications of the Genetic Architecture of Dilated Cardiomyopathy

Wilsbacher, Lisa D.

doi:10.1007/s11886-020-01423-w

Cited by 10 publications

(11 citation statements)

References 87 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies of human genetics have shown that there are multiple genes related to dilated cardiomyopathy (DCM) [ 26 – 29 ]. Based on RNA-Seq data obtained here from zebrafish heart, we summarized 30 DCM related genes homologous to human in zebrafish (Table 1 ), including cardiac actin, cardiac troponin, myosin heavy chain, myosin-binding protein, and so on.…”

Section: Resultsmentioning

confidence: 99%

Myocardial protective effect and transcriptome profiling of Naoxintong on cardiomyopathy in zebrafish

Liu

et al. 2021

Chin Med

View full text Add to dashboard Cite

Background Cardiomyopathy is a kind of cardiovascular diseases, which makes it more difficult for the heart to pump blood to other parts of the body, eventually leading to heart failure. Naoxintong (NXT), as a traditional Chinese Medicine (TCM) preparation, is widely used in the treatment of cardiovascular diseases, including cardiomyopathy, while its underlying mechanism has not been fully elucidated. The purpose of this study is to investigate the therapeutic effect of NXT on cardiomyopathy and its molecular mechanism in zebrafish model. Methods The zebrafish cardiomyopathy model was established using terfenadine (TFD) and treated with NXT. The therapeutic effect of NXT on cardiomyopathy was evaluated by measuring the heart rate, the distance between the sinus venosus and bulbus arteriosus (SV-BA), the pericardial area, and the blood flow velocity of zebrafish. Then, the zebrafish hearts were isolated and collected; transcriptome analysis of NXT on cardiomyopathy was investigated. Moreover, the heg1 mutant of zebrafish congenital cardiomyopathy model was used to further validate the therapeutic effect of NXT on cardiomyopathy. Additionally, UPLC analysis combined with the zebrafish model investigation was performed to identify the bioactive components of NXT. Results In the TFD-induced zebrafish cardiomyopathy model, NXT treatment could significantly restore the cardiovascular malformations caused by cardiac dysfunction. Transcriptome and bioinformatics analyses of the TFD and TFD + NXT treated zebrafish developing hearts revealed that the differentially expressed genes were highly enriched in biological processes such as cardiac muscle contraction and heart development. As a cardiac development protein associated with cardiomyopathy, HEG1 had been identified as one of the important targets of NXT in the treatment of cardiomyopathy. The cardiovascular abnormalities of zebrafish heg1 mutant could be recovered significantly from NXT treatment, including the expanded atrial cavity and blood stagnation. qRT-PCR analysis further showed that NXT could restore cardiomyopathy phenotype in zebrafish through HEG1-CCM signaling. Among the seven components identified in NXT, paeoniflorin (PF) and salvianolic acid B (Sal B) were considered to be the main bioactive ones with myocardial protection. Conclusion NXT presented myocardial protective effect and could restore myocardial injury and cardiac dysfunction in zebrafish; the action mechanism was involved in HEG1-CCM signaling.

show abstract

Section: Resultsmentioning

confidence: 99%

Myocardial protective effect and transcriptome profiling of Naoxintong on cardiomyopathy in zebrafish

Liu

et al. 2021

Chin Med

View full text Add to dashboard Cite

show abstract

“…Nowadays, individuals carrying RBM20 pathogenic variants are at a high risk of AR-DCM and early ICD implantation should be discussed [49]. We performed an exhaustive In 2012, Gu et al, reported an animal model with a deficient titin splicing identifying a loss-of-function mutation in RBM20 as the underlying cause for the pathological titin isoform expression.…”

Section: Rare Rbm20 Variants In Familial Dilated Cardiomyopathymentioning

confidence: 99%

“…Nowadays, individuals carrying RBM20 pathogenic variants are at a high risk of AR-DCM and early ICD implantation should be discussed [ 49 ]. We performed an exhaustive review of the literature concerning RBM20 and DCM published before October 2020.…”

Section: Rare Rbm20 Variants In Familial Dilatementioning

confidence: 99%

Malignant Arrhythmogenic Role Associated with RBM20: A Comprehensive Interpretation Focused on a Personalized Approach

Jordà

Toro

Díez

et al. 2021

JPM

View full text Add to dashboard Cite

The RBM20 gene encodes the muscle-specific splicing factor RNA-binding motif 20, a regulator of heart-specific alternative splicing. Nearly 40 potentially deleterious variants in RBM20 have been reported in the last ten years, being found to be associated with highly arrhythmogenic events in familial dilated cardiomyopathy. Frequently, malignant arrhythmias can be a primary manifestation of disease. The early recognition of arrhythmic genotypes is crucial in avoiding lethal episodes, as it may have an impact on the adoption of personalized preventive measures. Our study performs a comprehensive update of data concerning rare variants in RBM20 that are associated with malignant arrhythmogenic phenotypes with a focus on personalized medicine.

show abstract

“…DCM is characterized by left cardiac enlargement owing to left ventricular dilation as well as reduced systolic function, which is not secondary to ischemia, valvular disease, and hypertension. It may result in heart failure with a noticeable rate of morbidity and mortality 1 – 3 . The impaired systolic function is observed in the initial stages; however, diastolic dysfunction in association with reduced ejection fraction will be present in the advance stages 4 .…”

Section: Introductionmentioning

confidence: 99%

A novel causative functional mutation in GATA6 gene is responsible for familial dilated cardiomyopathy as supported by in silico functional analysis

Khazamipour

Gholampour-Faroji

Zeraati

et al. 2022

Sci Rep

View full text Add to dashboard Cite

Dilated cardiomyopathy (DCM), one of the most common types of cardiomyopathies has a heterogeneous nature and can be seen in Mendelian forms. Next Generation Sequencing is a powerful tool for identifying novel variants in monogenic disorders. We used whole-exome sequencing (WES) and Sanger sequencing techniques to identify the causative mutation of DCM in an Iranian pedigree. We found a novel variant in the GATA6 gene, leading to substituting Histidine by Tyrosine at position 329, observed in all affected family members in the pedigree, whereas it was not established in any of the unaffected ones. We hypothesized that the H329Y mutation may be causative for the familial pattern of DCM in this family. The predicted models of GATA6 and H329Y showed the high quality according to PROCHECK and ERRAT. Nonetheless, simulation results revealed that the protein stability decreased after mutation, while the flexibility may have been increased. Hence, the mutation led to the increased compactness of GATA6. Overall, these data indicated that the mutation could affect the protein structure, which may be related to the functional impairment of GATA6 upon H329Y mutation, likewise their involvement in pathologies. Further functional investigations would help elucidating the exact mechanism.

show abstract

Clinical Implications of the Genetic Architecture of Dilated Cardiomyopathy

Cited by 10 publications

References 87 publications

Myocardial protective effect and transcriptome profiling of Naoxintong on cardiomyopathy in zebrafish

Myocardial protective effect and transcriptome profiling of Naoxintong on cardiomyopathy in zebrafish

Malignant Arrhythmogenic Role Associated with RBM20: A Comprehensive Interpretation Focused on a Personalized Approach

A novel causative functional mutation in GATA6 gene is responsible for familial dilated cardiomyopathy as supported by in silico functional analysis

Contact Info

Product

Resources

About