Heart Failure ; genetics ; Humans ; Hypertrophy ; genetics ; MicroRNAs ; genetics

Heart failure (HF), a clinical syndrome with high morbidity and mortality, is becoming a growing public health problem. Dilated cardiomyopathy (DCM) is one of the major causes of HF, yet the molecular mechanisms underlying DCM-mediated HF are not completely understood. Previous studies have shown that dysregulation of arachidonic acid (AA) metabolism could contribute to the development of HF. To explore the roles of microRNAs (miRNAs) in regulating AA metabolism in HF, we used two public datasets to analyze the expression changes of miRNAs in the patients of DCM-mediated HF. A total of 101 and 88 miRNAs with significant abundance alterations in the two dataset were obtained, respectively. Around 1/3 of these miRNAs were predicted to target AA metabolic pathway genes. We also investigated the distribution of known single nucleotide polymorphisms (SNPs) within the sequences of miRNAs dysregulated in DCM-mediated HF patients, and identified miRNAs harboring high number of SNPs in either the seed regions or the entire sequences. These information could provide clues for further functional studies of miRNAs in the pathogeny of DCM-mediated HF.
Arachidonic Acid ; Cardiomyopathy, Dilated/genetics* ; Heart Failure/genetics* ; Humans ; MicroRNAs/genetics*

OBJECTIVE: To explore the genotype-phenotype correlation of a patient with cardio-facio-cutaneous syndrome (CFCS) due to variant of the MAP2K1 gene. METHODS: DNA was extracted from peripheral blood samples of the infant and his parents and subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing. RESULTS: The patient had typical CFCS facies and developmental delay, and was found to harbor a de novo heterozygous c.389A>G (p.Tyr130Cys) missense variant in exon 3 of the MAP2K1 gene. Based on the American college of Medical Genetics and Genomics guidelines, this variant was classified as likely pathogenic. CONCLUSION This patient has differed from previously reported cases by having no cardiac anomaly or seizures but typical facial features and skin abnormalities accompanied by growth retardation, intellectual impairment, and urinary malformation. It has therefore enriched the phenotypic spectrum of CFCS due to variants of the MAP2K1 gene.
Ectodermal Dysplasia/genetics* ; Facies ; Failure to Thrive/genetics* ; Heart Defects, Congenital ; Humans ; MAP Kinase Kinase 1/genetics* ; Mutation

Ca(2+) Mg(2+)-ATPase ; genetics ; Genetic Therapy ; Heart Failure ; therapy

BACKGROUND: Recent studies have reported circular RNA (circRNA) expression profiles in various tissue types; however, circRNA expression profile in human epicardial adipose tissue (EAT) remains undefined. This work aimed to compare circRNA expression patterns in EAT between the heart failure (HF) and non-HF groups. METHODS: RNA-sequencing was carried out to compare circRNA expression patterns in EAT specimens from coronary artery disease cases between the HF and non-HF groups. Quantitative real-time polymerase chain reaction was performed for validation. Comparisons of patient characteristics between the two groups were using t test, Mann-Whitney U test, and Chi-squared test. RESULTS: A total of 141 circRNAs substantially different between the HF and non-HF groups (P < 0.05; fold change >2) were detected, including 56 up-regulated and 85 down-regulated. Among them, hsa_circ_0005565 stood out, for it had the highest fold change and was significantly increased in HF patients in quantitative real-time polymerase chain reaction validation. The top highly expressed EAT circRNAs corresponded to genes involved in cell proliferation and inflammatory response, including GSE1, RHOBTB3, HIPK3, UBXN7, PCMTD1, N4BP2L2, CFLAR, EPB41L2, FCHO2, FNDC3B, and SPECC1. The top enriched Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway were positive regulation of metabolic processes and insulin resistance, respectively. CONCLUSION These data indicate EAT circRNAs may contribute to the pathogenesis of metabolic disorders causing HF.
Adipose Tissue ; Gene Ontology ; Heart Failure/genetics* ; Humans ; RNA, Circular ; Sequence Analysis, RNA

The association among plasma trimethylamine-N-oxide (TMAO), FMO3 polymorphisms, and chronic heart failure (CHF) remains to be elucidated. TMAO is a microbiota-dependent metabolite from dietary choline and carnitine. A prospective study was performed including 955 consecutively diagnosed CHF patients with reduced ejection fraction, with the longest follow-up of 7 years. The concentrations of plasma TMAO and its precursors, namely, choline and carnitine, were determined by liquid chromatography-mass spectrometry, and the FMO3 E158K polymorphisms (rs2266782) were genotyped. The top tertile of plasma TMAO was associated with a significant increment in hazard ratio (HR) for the composite outcome of cardiovascular death or heart transplantation (HR = 1.47, 95% CI = 1.13-1.91, P = 0.004) compared with the lowest tertile. After adjustments of the potential confounders, higher TMAO could still be used to predict the risk of the primary endpoint (adjusted HR = 1.33, 95% CI = 1.01-1.74, P = 0.039). This result was also obtained after further adjustment for carnitine (adjusted HR = 1.33, 95% CI = 1.01-1.74, P = 0.039). The FMO3 rs2266782 polymorphism was associated with the plasma TMAO concentrations in our cohort, and lower TMAO levels were found in the AA-genotype. Thus, higher plasma TMAO levels indicated increased risk of the composite outcome of cardiovascular death or heart transplantation independent of potential confounders, and the FMO3 AA-genotype in rs2266782 was related to lower plasma TMAO levels.
Carnitine ; Choline/metabolism* ; Chronic Disease ; Heart Failure/genetics* ; Humans ; Methylamines ; Oxygenases ; Prospective Studies

To explore the potential molecular mechanism of Mongolian medicine Bawei Sanxiang San in the treatment of chronic heart failure(CHF) through network pharmacology and molecular docking technology. The active ingredients and potential targets of Bawei Sanxiang San were collected by applying TCMSP, BATMAN databases and literature mining. CHF-related genes were collected through TTD, GeneCards and CTD databases. After the potential common targets between Bawei Sanxiang San and CHF were disco-vered, the interaction network diagram of "compound-target-pathway" was constructed using Cytoscape. The intersecting targets were imported into the DAVID database for GO function and KEGG pathway enrichment analysis. Finally, the Autodock_vina software was used to molecularly dock the selected proteins with the active ingredients of Bawei Sanxiang San. The results showed that there were 60 active ingredients in Bawei Sanxiang San that might be used to treat CHF, involving 311 target genes and 7 signaling pathways that directly related to CHF, such as HIF-1 signaling pathway, TNF signaling pathway, adrenergic signaling in cardiomyocytes, aldosterone-regulated sodium reabsorption, calcium signaling pathway, cGMP-PKG signaling pathway, renin secretion. Additionally, molecular docking showed that the bioactive compounds had good binding activity with the protein receptors of key target genes. Bawei Sanxiang San might exert therapeutic effects on CHF by regulating cardiomyocytes, angiogenic and inflammation related targets and pathways in a multi-component, multi-target and multi-pathway manner.
Drugs, Chinese Herbal ; Heart Failure/genetics* ; Humans ; Medicine, Chinese Traditional ; Medicine, Mongolian Traditional ; Molecular Docking Simulation

This study aimed to elucidate the effective components of Shengxian Decoction and its mechanism of action in treating chronic heart failure. Firstly, UHPLC-Q-TOF-MS was established to identify the main chemical constituents in the rat serum after intragastric administration with Shengxian Decoction. Secondly, the absorbed components in serum were then used for the network pharmacology analysis to infer the mechanism and effective components. Targets for constituents in serum were predicted at TCMSP and Swiss-TargetPrediction database. An association network map was drawn by network visualization software Cytoscape 3.6.1. Finally, GO enrichment analysis and KEGG pathway enrichment analysis were carried out for the core target genes. By UHPLC-Q-TOF-MS, 18 prototype compounds were definitely identified, including five compounds from Astragali Radix, four compounds from Anemarrhenae Rhizoma, four compounds from Bupleuri Radix, four compounds from Cimicifugae Rhizoma, and one compound from Platycodonis Radix. Those components of Shengxian Decoction were closely associated with 13 key protein targets, including inflammatory factors, like IL6, IL1 B, TNF, PTGS2, IL10; redox enzymes CAT, HMOX1, and MPO; cardiovascular targets, like VEGFA, NOS3, and NOS2; and transmememial proteins CAV1 and INS. Network pharmacology analysis showed that the 18 compounds could be responsible for the treatment of chronic heart failure by regulating HIF-1 signaling pathways, PI3 K-Akt signaling pathways, cGMP-PKG signaling pathways, cAMP signaling pathways and TNF signaling pathways. This study provided a scientific basis for mechanism and effective ingredients of Shengxian Decoction.
Animals ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Heart Failure/genetics* ; Rats ; Rhizome ; Signal Transduction

Ventricular myocardial non-compaction has been recognized and defined as a genetic cardiomyopathy by American Heart Association since 2006. The argument on the nomenclature and pathogenesis of this kind of ventricular myocardial non-compaction characterized by regional ventricular wall thickening and deep trabecular recesses often complicated with chronic heart failure, arrhythmia and thromboembolism and usually overlap the genetics and phenotypes of other kind of genetic or mixed cardiomyopathy still exist. The proper classification and correct nomenclature of the non-compact ventricles will contribute to the precisely and completely understanding of etiology and its related patho-physiological mechanism for a better risk stratification and more personalized therapy of the disease individually. All of the genetic heterogeneity and phenotypical overlap and the variety in histopathological, electromechanical and clinical presentation indicates that some of the cardiomyopathies might just be the different consequence of myocardial development variations related to gene mutation and phenotype of one or group genes induced by the interacted and disturbed process of gene modulation at different links of gene function expression and some other etiologies. This review aims to establish a new concept of "ventricular non-compaction syndrome" based on the demonstration of the current findings of etiology, epidemiology, histopathology and echocardiography related to the disorder of ventricular myocardial compaction and myocardial electromechanical function development.
American Heart Association ; Arrhythmias, Cardiac ; Cardiomyopathies* ; Classification ; Echocardiography ; Epidemiology ; Genetic Heterogeneity ; Genetics ; Heart Failure ; Humans ; Phenotype ; Thromboembolism

Cardio-facio-cutaneous (CFC) syndrome is an extremely rare autosomal dominant genetic disease due to BRAF and other gene mutations. The main characteristics of the patients are craniofacial deformities, cardiac malformations, skin abnormalities, delay of language and motor development, gastrointestinal dysfunction, intellectual disability, and epilepsy. In this case, the child has a typical CFC syndrome face and developmental delay. The gene results of the second-generation sequencing technology showed that there was a mutation site c.1741A>G (p. Asn581Asp) (heterozygous) in exon 14 of the BRAF (NM_004333.5) gene. The mutation was not observed in the child's parents. The above-mentioned mutation may be a de novo mutation. There is no effective therapy for this disease so far.
Abnormalities, Multiple ; Child ; Ectodermal Dysplasia/genetics* ; Facies ; Failure to Thrive ; Heart Defects, Congenital/genetics* ; Humans ; Mutation ; Proto-Oncogene Proteins B-raf/genetics*