- •Heart failure (HF) is a major public health problem worldwide; however, occurrence of HF in patients with underlying conditions has not been clearly unraveled.
- •In this study, we analyzed the whole exome and RNA sequencing data of patients with (HF) in comparison to healthy individuals to identify the pathways that are altered during occurrence of HF.
- •The results indicated dysregulation of phosphorylation and immune signalling pathways in HF, and identified mutations in TITIN, OBSCURIN, NOD2, CDH2, MAP3K5, and SLC17A4 that were associated with HF.
- •S100A12, S100A8, S100A9, PFDN5, and TMCC2, were found upregulated in patients with HF by RNA-Seq. OAS1 may be the key to be changed both by RNA-seq and WES. Our study revealed the key pathways and genes implicated in HF.
- •We believe that our study makes a significant contribution to the literature because the findings could identify overall disruption of key signalling pathways in patients with HF and suggested potential targets for clinical therapy.
Abbreviations:HF (heart failure), HFrEF (heart failure with reduced ejection fraction), HCM (hypertrophic cardiomyopathy), DCM (dilated cardiomyopathy), TNF (tumor necrosis factor), EF (ejection fraction), DEGs (differentially expressed genes), CNTs (controls), cTnI (cardiac troponin I), MAPK (mitogen-activated protein kinase), TTN (Titin), OBSCN (obscurin)
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
- Epidemiology of heart failure.Circ. Res. 2013; 113: 646-659
Ponikowski P, et al. Heart failure: preventing disease and death worldwide. ESC Heart Fail. 2014;11–135.
- Nutrition intervention in heart failure: should consumption of the DASH eating pattern be recommended to improve outcomes?.Heart Fail. Rev. 2019; 24: 565-573
- Aircraft, road and railway traffic noise as risk factors for heart failure and hypertensive heart disease—a case-control study based on secondary data.Int. J. Hyg. Environ. Health. 2016; 219: 749-758
- Genetic evaluation of cardiomyopathy—a Heart Failure Society of America practice guideline.J. Card. Fail. 2018; 24: 281-302
- Remodeling of the heart in hypertrophy in animal models with myosin essential light chain mutations.Front. Physiol. 2014; 22: 353
- Genotype-phenotype associations in dilated cardiomyopathy: meta-analysis on more than 8000 individuals.Clin. Res. Cardiol. 2017; 106: 127-139
- Novel phenotype–genotype correlations of hypertrophic cardiomyopathy caused by mutation in α-actin and myosin-binding protein genes in three unrelated Chinese families.J. Cardiol. 2019; 73: 438-444
- Mechanisms of disease: β-adrenergic receptors—alterations in signal transduction and pharmacogenomics in heart failure.Nat. Rev. Cardiol. 2005; 2: 475-483
- Kinases as therapeutic targets for heart failure.Nat. Rev. Drug Discov. 2003; 2: 99-113
- Proinflammatory cytokines in heart failure: double-edged swords.Heart Fail. Rev. 2010; 15: 543-562
- Brain TACE (tumor necrosis factor-α–converting enzyme) contributes to sympathetic excitation in heart failure rats.Hypertension. 2019; 74: 63-72
- Cytokines in heart failure.Adv. Clin. Chem. 2019; 93: 63-113
- A genetic link between risk for Alzheimer's disease and severe COVID-19 outcomes via the OAS1 gene.Brain. 2021; 144: 3727-3741
- Coming of age: ten years of next-generation sequencing technologies.Nat. Rev. Genet. 2016; 17: 333-351
- StringTie enables improved reconstruction of a transcriptome from RNA-seq reads.Nat. Biotechnol. 2015; 33: 290-295
- Differential regulation of protein phosphatase 1 (PP1) isoforms in human heart failure and atrial fibrillation.Basic Res. Cardiol. 2017; 112: 43
- Augmented phosphorylation of cardiac troponin I in hypertensive heart failure.J. Biol. Chem. 2012; 287: 848-857
- Innate immunity and the failing heart: the cytokine hypothesis revisited.Circ. Res. 2015; 116: 1254-1268
- Cardiac titin and heart disease.J. Cardiovasc. Pharmacol. 2014; 63: 207-212
- Obscurin variants and inherited cardiomyopathies.Biophys. Rev. 2017; 9: 239-243
- An ‘omics’ perspective on cardiomyopathies and heart failure.Trends Mol. Med. 2016; 22: 813-827
- Chromatin accessibility of human mitral valves and functional assessment of MVP risk loci.Circ. Res. 2021; 128: e84-e101
- Selective NOD1 agonists cause shock and organ injury/dysfunction in vivo.Am. J. Respir. Crit. Care Med. 2007; 175: 595-603
- Cadherin 2-related Arrhythmogenic cardiomyopathy: prevalence and clinical features.Circ. Genom. Precis. Med. 2021; 14e003097
- Circular RNA CircMAP3K5 acts as a MicroRNA-22-3p sponge to promote resolution of intimal hyperplasia via TET2-mediated smooth muscle cell differentiation.Circulation. 2021; 143: 354-371
- Sequencing of 2 subclinical atherosclerosis candidate regions in 3669 individuals: cohorts for heart and aging research in genomic epidemiology (CHARGE) consortium targeted sequencing study.Circ. Cardiovasc. Genet. 2014; 7: 359-364
- Determination of HLA-A, -B, -C, -DRB1 and -DQB1 Allele and Haplotype Frequencies in Heart Failure Patients.6(2). 2019: 388-395
- Phenotypic patterns of mononuclear cells in dilated cardiomyopathy.Circulation. 1995; 92: 2876-2885
- NOD2 and inflammation: current insights.J. Inflamm. Res. 2018; 11: 49-60
- S100 proteins as therapeutic targets.Biophys. Rev. 2018; 10: 1617-1629
- Usefulness of S100A12 as a prognostic biomarker for adverse events in patients with heart failure.Clin. Biochem. 2015; 48: 329-333
- Prevalence of the Prefoldin subunit 5 gene deletion in canine mammary tumors.PLoS One. 2015; 10e0131280
- S100A8/A9 complex as a new biomarker in prediction of mortality in elderly patients with severe heart failure.Int. J. Cardiol. 2012; 155: 26-32
- Ribosome biogenesis: a central player in cancer metastasis and therapeutic resistance.Cancer Res. 2022; (CAN-21-4087)
- I-allelic missense disease-causing variants in RPL3L associate neonatal dilated cardiomyopathy with muscle-specific ribosome biogenesis.Hum. Genet. 2020; 139: 1443-1454
- Recessive TAF1A mutations reveal ribosomopathy in siblings with end-stage pediatric dilated cardiomyopathy.Hum. Mol. Genet. 2017; 26: 2874-2881
- Heterozygous mutations in OAS1 cause infantile-onset pulmonary alveolar Proteinosis with Hypogammaglobulinemia.Am. J. Hum. Genet. 2018; 102: 480-486
- OAS1 rs1131454 genetic variant is associated with Alzheimer's disease: an epidemiological analysis.Brain. 2022; : awac132
- A Neanderthal OAS1 isoform protects individuals of European ancestry against COVID-19 susceptibility and severity.Nat. Med. 2021; 27: 659-667
- OAS1: a multiple sclerosis susceptibility gene that influences disease severity.Neurology. 2010; 75: 411-418
- Muscle-specific Cand2 is translationally upregulated by mTORC1 and promotes adverse cardiac remodeling.EMBO Rep. 2021; 22e52170
- Distinct epigenetic programs regulate cardiac myocyte development and disease in the human heart in vivo.Nat. Commun. 2018; 9: 391
- RPS27, a sORF-encoded polypeptide, functions Antivirally by activating the NF-κB pathway and interacting with viral envelope proteins in shrimp.Front. Immunol. 2019; 10: 2763
- Clinical and genetic fndings in patients with congenital cataract and heart diseases.Orphanet. J. Rare Dis. 2021; 16: 242
- Mapping of 79 loci for 83 plasma protein biomarkers in cardiovascular disease.PLoS Genet. 2017; 13e1006706