Evidence map›Paper›PMID 32755283›Full record

ArticleCirculation research2020

miR-18a Inhibits BMP4 and HIF-1α Normalizing Brain Arteriovenous Malformations.

Nagore I Marín-Ramos, Thu Zan Thein, Ketan B Ghaghada, Thomas C Chen, Steven L Giannotta, Florence M Hofman

Abstract read
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In one paragraph

Article in Circulation research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 2 pooled it
1.3field-weighted citation impact, top 15% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 29 citations in OpenAlex.

  1. Translational relevance of animal models available on brain arteriovenous malformations, a systematic review.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Pooled it
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  7. Delivery of Nucleic Acids for Vascular Tissue Engineering Applications.Regenerative engineering and translational medicine · 2025
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  10. Ang-1 and VEGF: central regulators of angiogenesis.Molecular and cellular biochemistry · 2025
    Review
  11. Review
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  13. NXPH4 mediated by mCellular & molecular biology letters · 2024
    Article
  14. Peripheral macrophages in the development and progression of structural cerebrovascular pathologies.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024
    Review
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  20. Review of treatment and therapeutic targets in brain arteriovenous malformation.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Nagore I Marín-RamosDepartments of Neurosurgery (N.I.M.-R., T.Z.T., T.C.C., S.L.G.), Keck School of Medicine, University of Southern California, Los Angeles.
Thu Zan TheinDepartments of Neurosurgery (N.I.M.-R., T.Z.T., T.C.C., S.L.G.), Keck School of Medicine, University of Southern California, Los Angeles.
Ketan B GhaghadaDepartment of Pediatric Radiology, Texas Children's Hospital, Houston (K.B.G.).
Thomas C ChenDepartments of Neurosurgery (N.I.M.-R., T.Z.T., T.C.C., S.L.G.), Keck School of Medicine, University of Southern California, Los Angeles.
Steven L GiannottaDepartments of Neurosurgery (N.I.M.-R., T.Z.T., T.C.C., S.L.G.), Keck School of Medicine, University of Southern California, Los Angeles.
Florence M HofmanDepartments of Pathology (T.C.C., F.M.H.), Keck School of Medicine, University of Southern California, Los Angeles.
University of Southern California · USTexas Children's Hospital · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

rationaleBrain arteriovenous malformations (AVMs) are abnormal tangles of vessels where arteries and veins directly connect without intervening capillary nets, increasing the risk of intracerebral hemorrhage and stroke. Current treatments are highly invasive and often not feasible. Thus, effective noninvasive treatments are needed. We previously showed that AVM-brain endothelial cells (BECs) secreted higher VEGF (vascular endothelial growth factor) and lower TSP-1 (thrombospondin-1) levels than control BEC; and that microRNA-18a (miR-18a) normalized AVM-BEC function and phenotype, although its mechanism remained unclear.

objectiveTo elucidate the mechanism of action and potential clinical application of miR-18a as an effective noninvasive treatment to selectively restore the phenotype and functionality of AVM vasculature. METHODS AND

resultsThe molecular pathways affected by miR-18a in patient-derived BECs and AVM-BECs were determined by Western blot, RT-qPCR (quantitative reverse transcription polymerase chain reaction), ELISA, co-IP, immunostaining, knockdown and overexpression studies, flow cytometry, and luciferase reporter assays. miR-18a was shown to increase TSP-1 and decrease VEGF by reducing PAI-1 (plasminogen activator inhibitor-1/SERPINE1) levels. Furthermore, miR-18a decreased the expression of BMP4 (bone morphogenetic protein 4) and HIF-1α (hypoxia-inducible factor 1α), blocking the BMP4/ALK (activin-like kinase) 2/ALK1/ALK5 and Notch signaling pathways. As determined by Boyden chamber assays, miR-18a also reduced the abnormal AVM-BEC invasiveness, which correlated with a decrease in MMP2 (matrix metalloproteinase 2), MMP9, and ADAM10 (ADAM metallopeptidase domain 10) levels. In vivo pharmacokinetic studies showed that miR-18a reaches the brain following intravenous and intranasal administration. Intranasal co-delivery of miR-18a and NEO100, a good manufacturing practices-quality form of perillyl alcohol, improved the pharmacokinetic profile of miR-18a in the brain without affecting its pharmacological properties. Ultra-high-resolution computed tomography angiography and immunostaining studies in an Mgp

conclusionsmiR-18a may have significant clinical value in preventing, reducing, and potentially reversing AVM.

Indexed as

Activin Receptors, Type IActivin Receptors, Type IIADAM10 ProteinAmyloid Precursor Protein SecretasesAnimalsBone Morphogenetic Protein 4BrainEndothelial CellsHumansHypoxia-Inducible Factor 1, alpha SubunitIntracranial Arteriovenous MalformationsMatrix Metalloproteinase 2Matrix Metalloproteinase 9Membrane ProteinsMiceMicroRNAsActivin Receptors, Type IActivin Receptors, Type IIACVR1 protein, humanACVRL1 protein, humanADAM10 ProteinADAM10 protein, humanAmyloid Precursor Protein SecretasesBMP4 protein, humanBone Morphogenetic Protein 4HIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitMatrix Metalloproteinase 2Matrix Metalloproteinase 9Membrane ProteinsMicroRNAsMIRN18A microRNA, humanMMP9 protein, humanMonoterpenesperillyl alcoholPlasminogen Activator Inhibitor 1Receptor, Transforming Growth Factor-beta Type ITGFBR1 protein, humanThrombospondin 1Vascular Endothelial Growth Factorsarteriovenous malformationBMP4endothelial cellsHIF-1αmir-18a

Identifiers

PMID32755283
OpenAlexW3047104614

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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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.