ArticleNature cardiovascular research2024
Nuclear ATP-citrate lyase regulates chromatin-dependent activation and maintenance of the myofibroblast gene program.
Article in Nature cardiovascular research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Engineered extracellular vesicles for ischemic heart diseases: modification methods, targeted delivery strategies, and multi-modal therapies - A systematic review.Frontiers in cardiovascular medicine · 2026Pooled it
- A metabolic-epigenetic switch governs multicellular cardiac repair following succinate dehydrogenase inhibition.Nature cardiovascular research · 2026Article
- Bioenergetic Materials for Tissue Regeneration: Modulating Metabolism to Promote Cellular Anabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Cardiac fibrosis: mechanistic insights and translational advances.Molecular biomedicine · 2026Review
- Acetyl-CoA-dependent processes are preferentially supported by local metabolite synthesis.Science advances · 2026Article
- Article
- Urea cycle fumarate limits fibrosis post-myocardial infarction by reducing fibroblast mitochondrial adenosine triphosphate production.Cardiovascular research · 2026Article
- ACLY-Driven Metabolic Reprogramming Promotes Histone Acetylation and Inflammation-Associated Fibrosis in Chronic Kidney Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Metabolic reprogramming in fibrosis-related diseases: underlying mechanisms and therapeutics.Molecular biomedicine · 2026Review
- Metabolic modulation of immune cell function: mechanisms and therapeutic implications in cancer immunotherapy.Oncogenesis · 2026Review
- Integrated epigenetic networks in aging: from histone to RNA modifications.Journal of translational medicine · 2026Review
- ATP-citrate lyase is a critical regulator of physiological and pathological angiogenesis.Angiogenesis · 2026Article
- Hallmarks of nuclear metabolism: implications for genome integrity, nuclear signaling, and therapeutic targeting.npj metabolic health and disease · 2026Review
- Mechanotyping of Organoids for Assessing Drug-Induced Injuries.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Metabolic reprogramming in cardiac fibrosis: mechanisms, crosstalk, and therapeutic interventions.Frontiers in physiology · 2026Review
- Metabolic programming in tooth development: a regulatory network from energy substrates to signaling instructions.Frontiers in cell and developmental biology · 2026Review
- TCA-cycle metabolites in the nucleus: drivers of chromatin and epigenetic control.BMC biology · 2025Review
- Reprogramming of Mitochondrial and Cellular Energy Metabolism in Fibroblasts and Cardiomyocytes: Mechanisms and Therapeutic Strategies in Cardiac Fibrosis.Journal of cardiovascular translational research · 2025Review
- Immunometabolism in heart failure.Nature reviews. Cardiology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
Abstract
Differentiation of cardiac fibroblasts to myofibroblasts is necessary for matrix remodeling and fibrosis in heart failure. We previously reported that mitochondrial calcium signaling drives α-ketoglutarate-dependent histone demethylation, promoting myofibroblast formation. Here we investigate the role of ATP-citrate lyase (ACLY), a key enzyme for acetyl-CoA biosynthesis, in histone acetylation regulating myofibroblast fate and persistence in cardiac fibrosis. We show that inactivation of ACLY prevents myofibroblast differentiation and reverses myofibroblasts towards quiescence. Genetic deletion of Acly in post-activated myofibroblasts prevents fibrosis and preserves cardiac function in pressure-overload heart failure. TGFβ stimulation enhances ACLY nuclear localization and ACLY-SMAD2/3 interaction, and increases H3K27ac at fibrotic gene loci. Pharmacological inhibition of ACLY or forced nuclear expression of a dominant-negative ACLY mutant prevents myofibroblast formation and H3K27ac. Our data indicate that nuclear ACLY activity is necessary for myofibroblast differentiation and persistence by maintaining histone acetylation at TGFβ-induced myofibroblast genes. These findings provide targets to prevent and reverse pathological fibrosis.
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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 OpenQuestion graph.