ArticleGenome biology2024
A feedback loop driven by H3K9 lactylation and HDAC2 in endothelial cells regulates VEGF-induced angiogenesis.
Article in Genome biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed.
- A relative methylation ordering biomarker of lactylation-related genes predicts prognosis and therapeutic response in cutaneous melanoma.Epigenetics · 2026Article
- Dynamic regulation of H3K9 modifications in cancer: pathogenesis and targeted therapies.Biomarker research · 2026Review
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- Lactate derived from CAFs mediates H3K18la in stemness gene promoters, which promotes tumor malignant phenotype formation.Molecular genetics and genomics : MGG · 2026Article
- Unveiling Lactylation: A Novel Frontier in Cancer Stemness and Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Lysine l-Lactylation: Bridging Metabolism, Chromatin and Disease.Cell proliferation · 2026Review
- Enhancing pulp regeneration through metabolic reprogramming of mature dental pulp stem cells mediated by GLUT1/HK2 mRNA delivery.International journal of oral science · 2026Article
- Protein lactylation in cancer: principles, programmes and therapeutic opportunities.Molecular cancer · 2026Review
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- Metabolomics in breast cancer: insights into treatment responses, disease progression, and prognostic assessment.Metabolomics : Official journal of the Metabolomic Society · 2026Review
- Lactylation-driven therapeutic resistance in cancer: Mechanisms and therapeutic opportunities.Genes & diseases · 2026Review
- Article
- Review
- Lactylation modification in extracellular vesicles: A key regulator of cellular communication.iScience · 2026Review
- Review
- Lysine lactylation-mediated post-translational modification: Molecular mechanisms and therapeutic target exploration in tumour drug resistance.Clinical and translational medicine · 2026Review
- Lactate metabolism and lactylation in cancer: from pathogenesis to therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Role and clinical importance of lactylation in tumors (Review).Molecular medicine reports · 2026Review
- NIPAL1 Drives a Metabolic-Epigenetic Feedback Loop to Promote Lactate-Mediated Immune Evasion in Esophageal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- From lactate to lactylation: novel pathological mechanisms and potential therapeutic targets for high-altitude cerebral oedema.Expert reviews in molecular medicine · 2026Review
34 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
backgroundVascular endothelial growth factor (VEGF) is one of the most powerful proangiogenic factors and plays an important role in multiple diseases. Increased glycolytic rates and lactate accumulation are associated with pathological angiogenesis.
resultsHere, we show that a feedback loop between H3K9 lactylation (H3K9la) and histone deacetylase 2 (HDAC2) in endothelial cells drives VEGF-induced angiogenesis. We find that the H3K9la levels are upregulated in endothelial cells in response to VEGF stimulation. Pharmacological inhibition of glycolysis decreases H3K9 lactylation and attenuates neovascularization. CUT& Tag analysis reveals that H3K9la is enriched at the promoters of a set of angiogenic genes and promotes their transcription. Interestingly, we find that hyperlactylation of H3K9 inhibits expression of the lactylation eraser HDAC2, whereas overexpression of HDAC2 decreases H3K9 lactylation and suppresses angiogenesis.
conclusionsCollectively, our study illustrates that H3K9la is important for VEGF-induced angiogenesis, and interruption of the H3K9la/HDAC2 feedback loop may represent a novel therapeutic method for treating pathological neovascularization.
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