ArticleClinical science (London, England : 1979)2025
A new mechanism of arterial calcification in diabetes: interaction between H3K18 lactylation and CHI3L1.
Article in Clinical science (London, England : 1979), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed.
- Vascular calcification: pathogenic mechanisms, signaling crosstalk and translational therapeutics.Signal transduction and targeted therapy · 2026Review
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- Lactylation and lactate: insights into muscle cell epigenetic regulators in exercise.Molecular medicine (Cambridge, Mass.) · 2026Review
- Identification and validation of lactylation-related diagnostic biomarkers for type 2 diabetes by WGCNA.Journal of clinical biochemistry and nutrition · 2026Article
- Progress of Research on the Metabolic Regulation of Lactylation in Muscle Tissues and Its Disease Associations.Biomolecules · 2026Review
- Unraveling the role of lactylation in cell death and correlative diseases: a comprehensive review.Frontiers in cell and developmental biology · 2026Review
- Histone lactylation: Unveiling a novel pathway for the impact of lactate on physiological and pathological processes (Review).International journal of molecular medicine · 2026Review
- Integrative transcriptomics and human tibial artery validation identifyJVS-vascular science · 2026Article
- Metabolic-epigenetic crosstalk in latent autoimmune diabetes in adults: potential roles of lactate-induced histone lactylation in immune regulation and pancreatic β-cell fate.Frontiers in endocrinology · 2026Review
- Automated assessment of breast arterial calcification: a new frontier in cardiovascular risk prediction.Frontiers in cardiovascular medicine · 2026Review
- Histone lactylation: a metabolic-epigenetic bridge linking glycolysis to salivary gland fibrosis in Sjögren's disease.Frontiers in immunology · 2026Review
- Lactylation Modification: From Basic Biological Process to Clinical Cardiovascular Diseases.Research (Washington, D.C.) · 2026Review
- Review
- Histone modifications in cervical cancer: Epigenetic mechanisms, functions and clinical implications (Review).Oncology reports · 2025Review
- Review
- Interleukin family in vascular calcification: molecular mechanisms and therapeutic perspectives.Frontiers in cardiovascular medicine · 2025Review
- Regulation of osteogenic differentiation in vascular smooth muscle cells under high-glucose condition.Frontiers in endocrinology · 2025Review
- Lactylation in diabetes mellitus and its complications: mechanisms of action and therapeutic potential - recent advances.Frontiers in endocrinology · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metabolic changes are an important characteristic of vascular complications in diabetes. The accumulation of lactate in the microenvironment can promote vascular smooth muscle cell (VSMC) calcification in diabetes, although the specific mechanism remains to be fully elucidated. In this study, we explored the characteristics of lactylation in diabetic arterial calcification and the underlying molecular mechanism. We found that in high-glucose calcified VSMC, the overall lactylation level was significantly increased. Mass spectrometry analysis revealed a significant up-regulation of H3 histone lactylation. After site-specific point-mutation at K18 to simulate the delactylation modification, VSMC calcification was significantly reduced. Through a combination of H3K18la ChIP-seq, RNA-seq, H3K18la ChIP-qPCR, and point-mutation experiments, we confirmed that H3K18la can up-regulate CHI3L1. CHI3L1 knockout significantly alleviated VSMC osteogenic phenotype transformation and mouse arterial calcification. RNA-seq analysis of the downstream molecular signaling showed that CHI3L1 activates the IL-13-IL-13Ra2-JAK1-STAT3 pathway. Targeted inhibition of IL-13Ra2 reduced VSMC calcification. We conclude that in a diabetic calcification environment, the H3 histone K18 site undergoes lactylation modification in VSMCs, upregulating CHI3L1, which, in turn, regulates the IL-13-IL-13Ra2-JAK1-STAT3 signaling pathway, ultimately exacerbating arterial calcification. Our study elucidates the epigenetic mechanism by which lactate promotes arterial calcification in diabetes.
Indexed as
Identifiers
What OpenQuestion holds
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.