ArticleEBioMedicine2019
Proteomics based identification of KDM5 histone demethylases associated with cardiovascular disease.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 46 citations in OpenAlex.
- Pharmacoepigenomic effects of anti-hypertensive drugs on DNA methylation and its implication to drug response and side effects.Epigenomics · 2025Article
- Roles of KDM5 demethylases in therapeutic resistance of cancers.Epigenetics & chromatin · 2025Review
- Current status and challenges of multi-omics research using animal models of atherosclerosis.Journal of molecular and cellular cardiology plus · 2025Review
- A Naturally Occurring Urinary Collagen Type I Alpha 1-Derived Peptide Inhibits Collagen Type I-Induced Endothelial Cell Migration at Physiological Concentrations.International journal of molecular sciences · 2025Article
- An exploratory study of high-throughput transcriptomic analysis reveals novel mRNA biomarkers for acute myocardial infarction using integrated methods.Scientific reports · 2025Article
- Current advances and future directions in targeting histone demethylases for cancer therapy.Molecules and cells · 2025Review
- Roles and mechanisms of histone methylation in vascular aging and related diseases.Clinical epigenetics · 2025Review
- Deletion of Transmembrane protein 184b leads to retina degeneration in mice.Cell proliferation · 2025Article
- Discovery of KDM5D as a novel biomarker for traumatic brain injury identified through bioinformatics analysis.Frontiers in immunology · 2025Article
- Role of histone post-translational modifications in atherosclerosis and the therapeutic potential of targeting epigenetic modifiers.Frontiers in cell and developmental biology · 2025Review
- Sex dimorphism and tissue specificity of gene expression changes in aging mice.Biology of sex differences · 2024Article
- Non-Coding RNA-Targeted Therapy: A State-of-the-Art Review.International journal of molecular sciences · 2024Review
- An Updated Review on the Significance of DNA and Protein Methyltransferases and De-methylases in Human Diseases: From Molecular Mechanism to Novel Therapeutic Approaches.Current medicinal chemistry · 2024Review
- Conversion of M1 Macrophages to Foam Cells: Transcriptome Differences Determined by Sex.Biomedicines · 2023Article
- Identification of Key Genes and Biological Pathways Related to Myocardial Infarction through Integrated Bioinformatics Analysis.Iranian journal of medical sciences · 2023Article
- Pharmacological Inhibition of Lysine-Specific Demethylase 1A Reduces Atherosclerotic Lesion Formation in Apolipoprotein E-Deficient Mice by a Mechanism Involving Decreased Oxidative Stress and Inflammation; Potential Implications in Human Atherosclerosis.Antioxidants (Basel, Switzerland) · 2022Article
- MicroRNAs as therapeutic targets in cardiovascular disease.The Journal of clinical investigation · 2022Review
- APEX2-Mediated Proximity Labeling Resolves the DDIT4-Interacting Proteome.International journal of molecular sciences · 2022Article
- Identification of Crucial Genes and Key Functions in Type 2 Diabetic Hearts by Bioinformatic Analysis.Frontiers in endocrinology · 2022Article
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Authors and funding
14 authors at 9 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe increased prevalence of cardiovascular disease (CVD) indicates a demand for novel therapeutic approaches. Proteome analysis of vascular tissues from animal models and humans with CVD could lead to the identification of novel druggable targets.
methodsLC-MS/MS analysis of thoracic aortas from three mouse models of non-diabetic and diabetic (streptozotocin (STZ)-induced) atherosclerosis followed by bioinformatics/pathway analysis was performed. Selected findings were confirmed by proteomics analysis of human vessels from patients with CVD as well as in vitro studies (migration, proliferation, angiogenesis assays) using endothelial (HUVEC) cells.
findingsComparative tissue proteomics of low density lipoprotein receptor deficient (Ldlr-/-) and diabetic Ldlr-/- (Ldlr-/-STZ) with wild type (WT) animals led to the identification of 284 differentially expressed proteins in both models. Among them, 177 proteins were also differentially expressed in diabetic apolipoprotein E deficient (ApoE-/-STZ) mice, suggesting expression changes associated with atherosclerosis independent of the model used. These proteins recapitulated the hallmarks of atherosclerosis. Comparison of these findings with differentially expressed proteins in human vessels with CVD enabled shortlisting of six commonly dysregulated proteins. Among them, lysine-specific demethylase 5D (KDM5D) exhibited pronounced overexpression accompanied by a reduction in the protein levels of its substrate, the trimethylated lysine 4 of histone H3 (H3K4me3), in patients with CVD. Functional interference studies applying a KDM5 inhibitor on HUVEC reduced cell proliferation, migration and tube-forming ability in vitro.
interpretationThis high-throughput proteomics strategy identified KDM5 histone demethylases being potentially involved in CVD, possibly by affecting H3K4 methylation. FUND: [SysVasc, HEALTH-2013 603288], [ERA-CVD PROACT: ANR-17-ECVD-0006, 01KL1805], [FRM, DEQ20170336759].
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