ArticleNature cardiovascular research2025
Large-scale multi-omics identifies drug targets for heart failure with reduced and preserved ejection fraction.
Article in Nature cardiovascular research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Cardiac proteomic and phosphoproteomic profiling defines clinically relevant molecular subgroups in human heart failure.Nature cardiovascular research · 2026Article
- Review
- Heart Failure with Reduced and Mildly Reduced Ejection Fraction: A Network Interpretive Framework of Mechanisms, Phenotypes, and Therapeutic Response.International journal of molecular sciences · 2026Review
- Molecular Mechanisms and Multi-Omics Integration in Heart Failure: From Pathophysiology to Precision Medicine.International journal of molecular sciences · 2026Review
- Amino Acid-Derived Metabolic Signature Across Stages of Systolic Dysfunction: Derivation and Internal Evaluation of the HASI (Heart Failure Amino Acid-Derived Systolic Index)-40 Index.International journal of molecular sciences · 2026Article
- Multi-Organ Physiologic Deficits During Exercise Identify Clinical and Molecular Predisposition to Heart Failure with Preserved Ejection Fraction.Circulation · 2026Article
- Genome-wide analysis of cardiac ventricular phenotypes reveals novel loci and therapeutic targets for heart failure.Nature communications · 2026Article
- Addressing Unmet Needs in Heart Failure with Preserved Ejection Fraction: Multi-Omics Approaches to Therapeutic Discovery.International journal of molecular sciences · 2026Review
- Combining mitochondrial proteomes and Mendelian randomization to identify novel therapeutic targets for diabetic nephropathy.Renal failure · 2025Article
- Drug and Clinical Candidate Drug Data in ChEMBL.Journal of medicinal chemistry · 2025Review
- Molecular Diagnostics in Heart Failure: From Biomarkers to Personalized Medicine.Diagnostics (Basel, Switzerland) · 2025Review
- Integrating multi-omics and machine learning strategies to explore the "gene-protein-metabolite" network in ischemic heart failure with Qi deficiency and blood stasis syndrome.Chinese medicine · 2025Article
- Drug Discovery and Development for Heart Failure Using Multi-Omics Approaches.International journal of molecular sciences · 2025Review
- Discovery of drug targets for heart failure with preserved and reduced ejection fraction.Nature cardiovascular research · 2025Article
Corrections and comments
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Authors and funding
29 authors.
Funding
Abstract
Heart failure (HF) has limited therapeutic options. In this study, we differentiated the pathophysiological underpinnings of the HF subtypes-HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF)-and uncovered subtype-specific therapeutic strategies. We investigated the causal roles of the human proteome and transcriptome using Mendelian randomization on more than 420,000 participants from the Million Veteran Program (27,799 HFrEF and 27,579 HFpEF cases). We created therapeutic target profiles covering efficacy, safety, novelty, druggability and mechanism of action. We replicated findings on more than 175,000 participants of diverse ancestries. We identified 70 HFrEF and 10 HFpEF targets, of which 58 were not previously reported; notably, the HFrEF and HFpEF targets are non-overlapping, suggesting the need for subtype-specific therapies. We classified 14 previously unclassified HF loci as HFrEF. We substantiated the role of ubiquitin-proteasome system, small ubiquitin-related modifier pathway, inflammation and mitochondrial metabolism in HFrEF. Among druggable genes, IL6R, ADM and EDNRA emerged as potential HFrEF targets, and LPA emerged as a potential target for both subtypes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.