ArticleJournal of neuro-oncology2019
Isocitrate dehydrogenase1 mutation reduces the pericyte coverage of microvessels in astrocytic tumours.
Article in Journal of neuro-oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Genetic Variants Impacting Angiogenesis Signaling Pathways in Glioblastoma Multiforme: A Systematic Review of Mutations and Polymorphisms.Current molecular medicine · 2024Pooled it
- Eppur si muove: the dynamic brain pericyte.Fluids and barriers of the CNS · 2025Review
- Abnormal changes in metabolites caused by mJournal of advanced research · 2025Review
- Pericytes in Glioblastoma: Hidden Regulators of Tumor Vasculature and Therapy Resistance.Cancers · 2024Review
- Genomic, epigenomic and transcriptomic landscape of glioblastoma.Metabolic brain disease · 2024Review
- Whole-tumor histogram analysis of synthetic magnetic resonance imaging predicts isocitrate dehydrogenase mutation status in gliomas.Quantitative imaging in medicine and surgery · 2024Article
- Diffusion along the perivascular space as a potential biomarker for glioma grading and isocitrate dehydrogenase 1 mutation status prediction.Quantitative imaging in medicine and surgery · 2023Article
- D-2-hydroxyglutarate regulates human brain vascular endothelial cell proliferation and barrier function.Journal of neuropathology and experimental neurology · 2023Article
- Anti-Vascular Endothelial Growth Factor Therapy Abolishes Glioma-Associated Endothelial Cell-Induced Tumor Invasion.Journal of molecular neuroscience : MN · 2023Article
- Gamma distribution model of diffusion MRI for evaluating the isocitrate dehydrogenase mutation status of glioblastomas.The British journal of radiology · 2022Article
- D-2-Hydroxyglutarate in Glioma Biology.Cells · 2021Review
- Tumor Vessels Fuel the Fire in Glioblastoma.International journal of molecular sciences · 2021Review
- Wild-Type IDH1 and Mutant IDH1 Opposingly Regulate Podoplanin Expression in Glioma.Translational oncology · 2020Article
- The MRI Features and Prognosis of Gliomas Associated With IDH1 Mutation: A Single Center Study in Southwest China.Frontiers in oncology · 2020Article
- Vessel Size Imaging is Associated with IDH Mutation and Patient Survival in Diffuse Lower-Grade Glioma.Cancer management and research · 2020Article
- Non-Invasive Estimation of GliomaFrontiers in oncology · 2020Article
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Authors and funding
25 authors at 6 institutions in 1 country.
Funding
Abstract
introductionTumour-associated angiogenesis is associated with the malignancy and poor prognosis of glioma. Isocitrate dehydrogenase (IDH) mutations are present in the majority of lower-grade (WHO grade II and III) and secondary glioblastomas, but their roles in tumour angiogenesis remain unclear.
methodsUsing magnetic resonance imaging (MRI), the cerebral blood flow (CBF) of IDH-mutated glioma was measured and compared with the IDH-wildtype glioma. The densities of microvessels in IDH-mutated and wildtype astrocytoma and glioblastoma were assessed by immunohistochemical (IHC) staining with CD34, and the pericytes were labelled with α-smooth muscle antigen (α-SMA), neural-glial antigen 2 (NG2) and PDGF receptor-β (PDGFR-β), respectively. Furthermore, glia-specific mutant IDH1 knock-in mice were generated to evaluate the roles of mutant IDH1 on brain vascular architectures. The transcriptions of the angiogenesis-related genes were assessed in TCGA datasets, including ANGPT1, PDGFB and VEGFA. The expressions of these genes were further determined by western blot in U87-MG cells expressing a mutant IDH1 or treated with 2-HG.
resultsThe MRI results indicated that CBF was reduced in the IDH-mutated gliomas. The IHC staining showed that the pericyte coverages of microvessels were significantly decreased, but the microvessel densities (MVDs) were only slightly decreased in IDH-mutated glioma. The mutant IDH1 knock-in also impeded the pericyte coverage of brain microvessels in mice. Moreover, the TCGA database showed the mRNA levels of angiogenesis factors, including ANGPT1, PDGFB and VEGFA, were downregulated, and their promoters were also highly hyper-methylated in IDH-mutated gliomas. In addition, both mutant IDH1 and D-2-HG could downregulate the expression of these genes in U87-MG cells.
conclusionsOur results suggested that IDH mutations could reduce the pericyte coverage of microvessels in astrocytic tumours by inhibiting the expression of angiogenesis factors. As vascular pericytes play an essential role in maintaining functional blood vessels to support tumour growth, our findings imply a potential avenue of therapeutic strategy for IDH-mutated gliomas.
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