ArticleJournal of molecular cell biology2023
Histone lactylation driven by mROS-mediated glycolytic shift promotes hypoxic pulmonary hypertension.
Article in Journal of molecular cell biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
89 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- Lactylation and its roles in diseases: a systematic bibliometric exploration of the research landscape.Frontiers in oncology · 2025Pooled it
- Lactylation: Metabolic epigenetic regulation and cell death mechanisms in myocardial ischemia‒reperfusion injury.Genes & diseases · 2027Review
- Lactate as a predictive biomarker and therapeutic target in cardiopulmonary bypass-associated acute kidney injury.iScience · 2026Article
- Lactylation at the metabolic-epigenetic interface in cardiovascular diseases: context-dependent mechanisms and translational roadmap.Journal of advanced research · 2026Review
- Secretory Carrier Membrane Protein 3 Knockdown Attenuates Hypoxic Pulmonary Hypertension Potentially Involving WW Domain-Containing E3 Ubiquitin Protein Ligase 1.Biochemical genetics · 2026Article
- Lysine l-Lactylation: Bridging Metabolism, Chromatin and Disease.Cell proliferation · 2026Review
- Lactylation modification: a new bridge connecting macrophage metabolism and pulmonary hypertension.Applied microbiology and biotechnology · 2026Review
- Hypoxia-injured pulmonary vascular targeting and microenvironment-responsive nanoparticle to treat hypoxic pulmonary hypertension.Journal of nanobiotechnology · 2026Article
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- The role of γ-aminobutyric acid and its receptor in metabolic reprogramming and tumor progression.Biochemistry and biophysics reports · 2026Review
- Lactylation and lactate: insights into muscle cell epigenetic regulators in exercise.Molecular medicine (Cambridge, Mass.) · 2026Review
- Data Resources and Computational Methods for Lactylation Site Prediction: A Mini-Review.International journal of molecular sciences · 2026Review
- Article
- Histone H3K9 lactylation activates the TXNIP/NLRP3 pathway to drive macrophage inflammation after spinal cord injury.Redox biology · 2026Article
- OSA Initiates Histone Lactylation That Drives PDE4B/FUS/AGT Axis to Pulmonary Hypertension.Cell proliferation · 2026Article
- Histone Modifications in Cardiovascular Disease: Mechanisms and Therapeutic Opportunities.MedComm · 2026Review
- LDHA protects vascular endothelial cells from oxidative stress‑induced mitochondrial damage via HIF‑1α activation and glycolytic reprogramming.Molecular medicine reports · 2026Article
- From Byproduct to Regulator: The Expanding Role of Lactate and Lactylation in Cardiovascular Physiology and Disease.Biology · 2026Review
- From lactate to lactylation: novel pathological mechanisms and potential therapeutic targets for high-altitude cerebral oedema.Expert reviews in molecular medicine · 2026Review
- Lactylation formation, gene regulation, biological functions, and clinical relevance.Histology and histopathology · 2026Review
29 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increased mitochondrial reactive oxygen species (mROS) and glycolysis have been established in pulmonary hypertension (PH). However, the effect of elevated mROS on glycolytic shift and how increased glycolysis promotes hypoxic pulmonary artery smooth muscle cell (PASMC) proliferation and vascular remodeling remain elusive. Here, we reported that hypoxia-induced mROS inhibit HIF-1α hydroxylation and further trigger PASMC glycolytic switch through the upregulated HIF-1α/PDK1&PDK2/p-PDH-E1α axis, which facilitates lactate accumulation and histone lactylation. Through H3K18la and HIF-1α ChIP-seq analysis, we found that the enhanced histone lactylation of HIF-1α targets, such as Bmp5, Trpc5, and Kit, promotes PASMC proliferation. Knockdown of Pdk1&2 blunts lactate production, histone lactylation marks, and PASMC proliferation. Moreover, pharmacological intervention with lactate dehydrogenase inhibitor diminishes histone lactylation and ameliorates PASMC proliferation and vascular remodeling in hypoxic PH rats. Taken together, this study provides proof of concept for anti-remodeling therapy through lactate manipulation.
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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.