ArticleGenome medicine2024
Integrating metabolomics and proteomics to identify novel drug targets for heart failure and atrial fibrillation.
Article in Genome medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Multi-omics profiling of circulating proteins and metabolites in persistent atrial fibrillation: VDAC1 identified as a candidate circulating protein.International journal of cardiology. Heart & vasculature · 2026Article
- Identification of key molecules and pathways in CaOx crystal-induced renal injury based on metabolomics and proteomics.International urology and nephrology · 2026Article
- Metabolic Signatures of Atrial Functional Impairment in Paroxysmal Atrial Fibrillation Patients: A CMR Strain-metabolomics Study.Journal of cardiovascular translational research · 2026Article
- Article
- ACOT1-specific expression modulates metabolic reprogramming in diabetic cardiomyopathy: The role of SREBP1c lactylation in CD36-mediated lipotoxicity.American heart journal plus : cardiology research and practice · 2026Article
- Analysis of whole genome sequencing and plasma metabolomics unveil genetic determinants and clinical implications for human health.Nature communications · 2026Article
- Innovative Advances in Non-Invasive Detection Technologies for Heart Failure: Synergistic Application of Multimodal Sensing and Intelligent Algorithms.Reviews in cardiovascular medicine · 2026Review
- Multi-Omics Identification of Biomarkers for High-Altitude Pulmonary Hypertension.Journal of cardiovascular development and disease · 2026Article
- Circulating cardiometabolic metabolite profiles associated with ambient air pollution and atrial fibrillation risk: a prospective cohort study.Cardiovascular diabetology · 2026Article
- MicroRNAs in Heart Failure Pathogenesis and Progression: Mechanistic Control, Biomarker Potential, and Translational Perspectives.Life (Basel, Switzerland) · 2026Review
- Challenges and Opportunities in Multi-Omics Data Acquisition and Analysis: Toward Integrative Solutions.Biomolecules · 2026Review
- Metabolic Drivers of Valve Calcification and Atrial Remodeling in Calcific Aortic Stenosis.Biomolecules · 2026Review
- Diagnostic Potential of Metabolomic and Proteomic Biomarkers in Cardiology-A Narrative Review.Biomedicines · 2026Review
- Integrated Multiomics Analysis Reveals Manual Therapy Restores Autophagic Homeostasis via the AMPK/ULK1 Axis in Chronic Low Back Pain.Pain research & management · 2026Article
- Unraveling the Lipidomic Determinants of Atrial Fibrillation: An Extensive Mendelian Randomization StudyEndocrine, metabolic & immune disorders drug targets · 2026Article
- Glucokinase activator, circulating metabolites, and cardio-cerebrovascular diseases: a Mendelian randomization study.Cardiovascular diabetology · 2025Article
- Genomic medicine for heart failure prediction in patients with atrial fibrillation.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2025Article
- Identification of potential therapeutic drug targets for sepsis by combining the human plasma proteome and genome: a Mendelian randomization study.Journal of thoracic disease · 2025Article
- Metabolic reprogramming in the post-metastatic tumor microenvironment: multi-omics insights into determinants of immunotherapy response.Frontiers in immunology · 2025Review
- Metabolic phenotypes: Molecular bridges between health homeostasis and disease imbalance.Computational and structural biotechnology journal · 2025Review
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Authors and funding
8 authors.
Funding
Abstract
backgroundAltered metabolism plays a role in the pathophysiology of cardiac diseases, such as atrial fibrillation (AF) and heart failure (HF). We aimed to identify novel plasma metabolites and proteins associating with cardiac disease.
methodsMendelian randomisation (MR) was used to assess the association of 174 metabolites measured in up to 86,507 participants with AF, HF, dilated cardiomyopathy (DCM), and non-ischemic cardiomyopathy (NICM). Subsequently, we sourced data on 1567 plasma proteins and performed cis MR to identify proteins affecting the identified metabolites as well as the cardiac diseases. Proteins were prioritised on cardiac expression and druggability, and mapped to biological pathways.
resultsWe identified 35 metabolites associating with cardiac disease. AF was affected by seventeen metabolites, HF by nineteen, DCM by four, and NCIM by taurine. HF was particularly enriched for phosphatidylcholines (p = 0.029) and DCM for acylcarnitines (p = 0.001). Metabolite involvement with AF was more uniform, spanning for example phosphatidylcholines, amino acids, and acylcarnitines. We identified 38 druggable proteins expressed in cardiac tissue, with a directionally concordant effect on metabolites and cardiac disease. We recapitulated known associations, for example between the drug target of digoxin (AT1B2), taurine and NICM risk. Additionally, we identified numerous novel findings, such as higher RET values associating with phosphatidylcholines and decreasing AF and HF. RET is targeted by drugs such as regorafenib which has known cardiotoxic side-effects. Pathway analysis implicated involvement of GDF15 signalling through RET, and ghrelin regulation of energy homeostasis in cardiac pathogenesis.
conclusionsThis study identified 35 plasma metabolites involved with cardiac diseases and linked these to 38 druggable proteins, providing actionable leads for drug development.
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