The Evolving Story in the Genetic Analysis for Heart Failure

Miyazawa, Kazuo; Ito, Kei

doi:10.3389/fcvm.2021.646816

Cited by 4 publications

(2 citation statements)

References 33 publications

(34 reference statements)

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“…Several disease-susceptibility loci of heart failure and cardiomyopathies have been identified in genome wide association studies ( 56 ). However, these loci were either not identified as DEGs in our study or they were only differentially expressed in proteomic analysis.…”

Section: Discussionmentioning

confidence: 99%

Multi-omics integration to identify the genetic expression and protein signature of dilated and ischemic cardiomyopathy

Portokallidou

Dovrolis²,

Ragia³

et al. 2023

Front. Cardiovasc. Med.

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IntroductionHeart failure (HF) is a complex clinical syndrome leading to high morbidity. In this study, we aimed to identify the gene expression and protein signature of HF main causes, namely dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM).MethodsOmics data were accessed through GEO repository for transcriptomic and PRIDE repository for proteomic datasets. Sets of differentially expressed genes and proteins comprising DCM (DiSig) and ICM (IsSig) signatures were analyzed by a multilayered bioinformatics approach. Enrichment analysis via the Gene Ontology was performed through the Metascape platform to explore biological pathways. Protein-protein interaction networks were analyzed via STRING db and Network Analyst.ResultsIntersection of transcriptomic and proteomic analysis showed 10 differentially expressed genes/proteins in DiSig (AEBP1, CA3, HBA2, HBB, HSPA2, MYH6, SERPINA3, SOD3, THBS4, UCHL1) and 15 differentially expressed genes/proteins in IsSig (AEBP1, APOA1, BGN, CA3, CFH, COL14A1, HBA2, HBB, HSPA2, LTBP2, LUM, MFAP4, SOD3, THBS4, UCHL1). Common and distinct biological pathways between DiSig and IsSig were retrieved, allowing for their molecular characterization. Extracellular matrix organization, cellular response to stress and transforming growth factor-beta were common between two subphenotypes. Muscle tissue development was dysregulated solely in DiSig, while immune cells activation and migration in IsSig.DiscussionOur bioinformatics approach sheds light on the molecular background of HF etiopathology showing molecular similarities as well as distinct expression differences between DCM and ICM. DiSig and IsSig encompass an array of “cross-validated” genes at both transcriptomic and proteomic level, which can serve as novel pharmacological targets and possible diagnostic biomarkers.

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Section: Discussionmentioning

confidence: 99%

Multi-omics integration to identify the genetic expression and protein signature of dilated and ischemic cardiomyopathy

Portokallidou

Dovrolis²,

Ragia³

et al. 2023

Front. Cardiovasc. Med.

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“…The genetic analysis of the causes and trajectory of heart failure has made slower progress than that for other forms of heart disease like coronary artery disease or atrial fibrillation [13]. This is partly because heart failure may have a variety of causes, including chronic hypertension, valvular disease, ischaemic heart disease, infectious diseases, congenital heart diseases and hereditary cardiomyopathies, all of which reach a common endpoint pathology.…”

mentioning

confidence: 99%

Gene variants of the renin angiotensin aldosterone system for risk stratification in heart disease

Palmer

2021

Kardiol Pol

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Dissecting Regulatory Non-Coding Heart Disease GWAS Loci with High-Resolution 3D Chromatin Interactions Reveals Causal Genes with Pathophysiological Relevance to Heart Failure

Gill,

Lu,

Eres

et al. 2024

Preprint

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Heart failure is caused in part by cardiac remodeling processes that include the death of cardiac myocytes and their replacement by cardiac fibroblasts. We hypothesized that these two cell types may harbor epigenetic contexts in which heart disease-associated non-coding SNPs perturb gene expression relevant to disease. Accordingly, we generated high-resolution Hi-C data layered with functional genomic information to annotate and link putative distal regulatory elements in heart disease-associated loci to gene promoters. Our analysis identified several target genes with established roles in cardiac fibrosis and/or heart disease (GJA1, TBC1D32, CXCL12, IL6R, and FURIN). Perturb-seq in cardiac fibroblasts after knocking out putative regulatory elements confirmed regulatory relationships involving GJA1, CXCL12, and FURIN, in addition to changes in transcriptomic signatures associated with fibroblasts in heart failure. Our results demonstrate how integrative multi-omic approaches can delineate pathophysiologically relevant regulatory circuits that connect protein-coding genes to non-coding genetic variants associated with disease.

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The Evolving Story in the Genetic Analysis for Heart Failure

Cited by 4 publications

References 33 publications

Multi-omics integration to identify the genetic expression and protein signature of dilated and ischemic cardiomyopathy

Multi-omics integration to identify the genetic expression and protein signature of dilated and ischemic cardiomyopathy

Gene variants of the renin angiotensin aldosterone system for risk stratification in heart disease

Dissecting Regulatory Non-Coding Heart Disease GWAS Loci with High-Resolution 3D Chromatin Interactions Reveals Causal Genes with Pathophysiological Relevance to Heart Failure

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