ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
EZH2 modulates angiogenesis in vitro and in a mouse model of limb ischemia.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 65 citations in OpenAlex.
- Polycomb Repressive Complex 2 drives flow-sensitive endothelial states underlying vascular inflammation and disease.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Disruption of PRC1 components RING1A and RING1B promotes angiogenesis via relieving BMP4 repression.Journal of advanced research · 2026Article
- LncRNA KCNQ1OT1 aggravates myocardial ischemia/reperfusion injury by mediating the EZH2/TIMP-3 axis.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026Article
- LncRNA SNHG14 Regulates the Expression of BDNF by Recruiting Histone Methyltransferase EZH2 to Mediate H3K27me3, Thereby Affecting Angiogenesis and Functional Recovery After Cerebral Ischemia.Molecular neurobiology · 2025Article
- Review
- S-nitrosylation of EZH2 alters PRC2 assembly, methyltransferase activity, and EZH2 stability to maintain endothelial homeostasis.Nature communications · 2025Article
- EZH2 Inhibition to Counteract Oral Cancer Progression through Wnt/β-Catenin Pathway Modulation.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Control of endothelial cell function and arteriogenesis by MEG3:EZH2 epigenetic regulation of integrin expression.Molecular therapy. Nucleic acids · 2024Article
- Enhancer of zeste homolog 2 facilitates phenotypic transition of vascular smooth muscle cells leading to aortic aneurysm/dissection.Experimental and therapeutic medicine · 2024Article
- Inhibition of the histone methyltransferase EZH2 induces vascular stiffness.Clinical science (London, England : 1979) · 2024Article
- Epigenetic control of vascular endothelial function revealed by multi-omics.European heart journal · 2024Article
- The involvement of RNA N6-methyladenosine and histone methylation modification in decidualization and endometriosis-associated infertility.Clinical and translational medicine · 2024Article
- H3K27Me3 abundance increases fibrogenesis during endothelial-to-mesenchymal transition via the silencing of microRNA-29c.Frontiers in cardiovascular medicine · 2024Article
- Assessment of the Therapeutic Potential of Enhancer of Zeste Homolog 2 Inhibition in a Murine Model of Bronchiolitis Obliterans Syndrome.Transplant international : official journal of the European Society for Organ Transplantation · 2024Article
- Smooth muscle mineralocorticoid receptor as an epigenetic regulator of vascular ageing.Cardiovascular research · 2023Article
- Optimizing Concentration of Polyethelene Glycol for Exosome Isolation from Plasma for Downstream Application.Medicina (Kaunas, Lithuania) · 2022Article
- Long Non-Coding RNA Regulation of Epigenetics in Vascular Cells.Non-coding RNA · 2021Review
- Serum-Derived Small Extracellular Vesicles From Diabetic Mice Impair Angiogenic Property of Microvascular Endothelial Cells: Role of EZH2.Journal of the American Heart Association · 2021Article
- Epigenetic Regulations of Microglia/Macrophage Polarization in Ischemic Stroke.Frontiers in molecular neuroscience · 2021Review
- MiRNAs in Gestational Diabetes Mellitus: Potential Mechanisms and Clinical Applications.Journal of diabetes research · 2021Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Epigenetic mechanisms may regulate the expression of pro-angiogenic genes, thus affecting reparative angiogenesis in ischemic limbs. The enhancer of zest homolog-2 (EZH2) induces thtrimethylation of lysine 27 on histone H3 (H3K27me3), which represses gene transcription. We explored (i) if EZH2 expression is regulated by hypoxia and ischemia; (ii) the impact of EZH2 on the expression of two pro-angiogenic genes: eNOS and BDNF; (iii) the functional effect of EZH2 inhibition on cultured endothelial cells (ECs); (iv) the therapeutic potential of EZH2 inhibition in a mouse model of limb ischemia (LI). EZH2 expression was increased in cultured ECs exposed to hypoxia (control: normoxia) and in ECs extracted from mouse ischemic limb muscles (control: absence of ischemia). EZH2 increased the H3K27me3 abundance onto regulatory regions of eNOS and BDNF promoters. In vitro RNA silencing or pharmacological inhibition by 3-deazaneplanocin (DZNep) of EZH2 increased eNOS and BDNF mRNA and protein levels and enhanced functional capacities (migration, angiogenesis) of ECs under either normoxia or hypoxia. In mice with experimentally induced LI, DZNep increased angiogenesis in ischaemic muscles, the circulating levels of pro-angiogenic hematopoietic cells and blood flow recovery. Targeting EZH2 for inhibition may open new therapeutic avenues for patients with limb ischemia.
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