ArticleCardiovascular research2018
DNA methylation of a PLPP3 MIR transposon-based enhancer promotes an osteogenic programme in calcific aortic valve disease.
Article in Cardiovascular research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
- Decoding lysophosphatidic acid signaling in physiology and disease: mapping the multimodal and multinodal signaling networks.Signal transduction and targeted therapy · 2025Review
- Navigating the Landscape of Translational Medicine of Calcific Aortic Valve Disease: Bridging Bench to Bedside.JACC. Asia · 2025Review
- Calcific aortic stenosis: omics-based target discovery and therapy development.European heart journal · 2025Review
- CRISPR/dCas9-Mediated DNA Methylation Editing onInternational journal of molecular sciences · 2024Article
- Epigenetic age acceleration and risk of aortic valve stenosis: a bidirectional Mendelian randomization study.Clinical epigenetics · 2024Article
- CRISPR/Cas9 technology: applications in oocytes and early embryos.Journal of translational medicine · 2023Review
- Calcific aortic valve disease: mechanisms, prevention and treatment.Nature reviews. Cardiology · 2023Review
- Increasing Specificity of Targeted DNA Methylation Editing by Non-Enzymatic CRISPR/dCas9-Based Steric Hindrance.Biomedicines · 2023Review
- Toward the Development of Epigenome Editing-Based Therapeutics: Potentials and Challenges.International journal of molecular sciences · 2023Review
- Network-Guided Multiomic Mapping of Aortic Valve Calcification.Arteriosclerosis, thrombosis, and vascular biology · 2023Review
- Enzyme-free targeted DNA demethylation using CRISPR-dCas9-based steric hindrance to identify DNA methylation marks causal to altered gene expression.Nature protocols · 2022Review
- Implication of Lipids in Calcified Aortic Valve Pathogenesis: Why Did Statins Fail?Journal of clinical medicine · 2022Review
- Calcific aortic valve disease: from molecular and cellular mechanisms to medical therapy.European heart journal · 2022Article
- Article
- Multi-Omics Approaches to Define Calcific Aortic Valve Disease Pathogenesis.Circulation research · 2021Review
- Proteomic Architecture of Valvular Extracellular Matrix: FNDC1 and MXRA5 Are New Biomarkers of Aortic Stenosis.JACC. Basic to translational science · 2021Article
- CRISPR technologies for precise epigenome editing.Nature cell biology · 2021Review
- Dead Cas Systems: Types, Principles, and Applications.International journal of molecular sciences · 2019Review
- Autotaxin and Lipoprotein Metabolism in Calcific Aortic Valve Disease.Frontiers in cardiovascular medicine · 2019Review
- The Genetic Regulation of Aortic Valve Development and Calcific Disease.Frontiers in cardiovascular medicine · 2018Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aims: Calcific aortic valve disease (CAVD) is characterized by the osteogenic transition of valve interstitial cells (VICs). In CAVD, lysophosphatidic acid (LysoPA), a lipid mediator with potent osteogenic activity, is produced in the aortic valve (AV) and is degraded by membrane-associated phospholipid phosphatases (PLPPs). We thus hypothesized that a dysregulation of PLPPs could participate to the osteogenic reprograming of VICs during CAVD. Methods and results: The expression of PLPPs was examined in human control and mineralized AVs and comprehensive analyses were performed to document the gene regulation and impact of PLPPs on the osteogenic transition of VICs. We found that PLPP3 gene and enzymatic activity were downregulated in mineralized AVs. Multidimensional gene profiling in 21 human AVs showed that expression of PLPP3 was inversely correlated with the level of 5-methylcytosine (5meC) located in an intronic mammalian interspersed repeat (MIR) element. Bisulphite pyrosequencing in a larger series of 67 AVs confirmed that 5meC in intron 1 was increased by 2.2-fold in CAVD compared with control AVs. In isolated cells, epigenome editing with clustered regularly interspersed short palindromic repeats-Cas9 system containing a deficient Cas9 fused with DNA methyltransferase (dCas9-DNMT) was used to increase 5meC in the intronic enhancer and showed that it reduced significantly the expression of PLPP3. Knockdown experiments showed that lower expression of PLPP3 in VICs promotes an osteogenic programme. Conclusions: DNA methylation of a MIR-based enhancer downregulates the expression of PLPP3 and promotes the mineralization of the AV.
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