Evidence map›Paper›PMID 24837588›Full record

ArticleJournal of the American Heart Association2014

Argonaute-2 promotes miR-18a entry in human brain endothelial cells.

Raquel Ferreira, Tiago Santos, Arun Amar, Alex Gong, Thomas C Chen, Stanley M Tahara, Steven L Giannotta, Florence M Hofman

Open access · goldAbstract read
In one paragraph

Article in Journal of the American Heart Association, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
0.4field-weighted citation impact, top 35% 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

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.

  1. Pooled it
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  3. Widespread tissue delivery of antagomiRs via intramuscular administration.Molecular therapy. Methods & clinical development · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Raquel FerreiraDepartment of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA (R.F., A.A., T.C.C., S.L.G., F.M.H.).
Tiago SantosDepartment of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA (T.S., A.G., T.C.C., F.M.H.).
Arun AmarDepartment of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA (R.F., A.A., T.C.C., S.L.G., F.M.H.).
Alex GongDepartment of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA (T.S., A.G., T.C.C., F.M.H.).
Thomas C ChenDepartment of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA (R.F., A.A., T.C.C., S.L.G., F.M.H.) Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA (T.S., A.G., T.C.C., F.M.H.).
Stanley M TaharaDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA (S.M.T.).
Steven L GiannottaDepartment of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA (R.F., A.A., T.C.C., S.L.G., F.M.H.).
Florence M HofmanDepartment of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA (R.F., A.A., T.C.C., S.L.G., F.M.H.) Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA (T.S., A.G., T.C.C., F.M.H.).
University of Southern California · USNeurological Surgery · US

Funding

PlGF-HIF1a-miRNA Axis in Sickle Pulmonary HypertensionR01HL111372 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI KALRA, VIJAY K., MALIK, PUNAM · 2012 to 2016
$3.1M
NHLBI NIH HHS HL111372NHLBI NIH HHS R01 HL111372
6 · The paper itself

Abstract

backgroundCerebral arteriovenous malformation (AVM) is a vascular disease exhibiting abnormal blood vessel morphology and function. miR-18a ameliorates the abnormal characteristics of AVM-derived brain endothelial cells (AVM-BEC) without the use of transfection reagents. Hence, our aim was to identify the mechanisms by which miR-18a is internalized by AVM-BEC. Since AVM-BEC overexpress RNA-binding protein Argonaute-2 (Ago-2) we explored the clinical potential of Ago-2 as a systemic miRNA carrier. METHODS AND

resultsPrimary cultures of AVM-BEC were isolated from surgical specimens and tested for endogenous miR-18a levels using qPCR. Conditioned media (CM) was derived from AVM-BEC cultures (AVM-BEC-CM). AVM-BEC-CM significantly enhanced miR-18a internalization. Ago-2 was detected using western blotting and immunostaining techniques. Ago-2 was highly expressed in AVM-BEC; and siAgo-2 decreased miR-18a entry into brain-derived endothelial cells. Only brain-derived endothelial cells were responsive to the Ago-2/miR-18a complex and not other cell types tested. Secreted products (eg, thrombospondin-1 [TSP-1]) were tested using ELISA. Brain endothelial cells treated with the Ago-2/miR-18a complex in vitro increased TSP-1 secretion. In the in vivo angiogenesis glioma model, animals were treated with miR-18a in combination with Ago-2. Plasma was obtained and tested for TSP-1 and vascular endothelial growth factor (VEGF)-A. In this angiogenesis model, the Ago-2/miR-18a complex caused a significant increase in TSP-1 and decrease in VEGF-A secretion in the plasma.

conclusionsAgo-2 facilitates miR-18a entry into brain endothelial cells in vitro and in vivo. This study highlights the clinical potential of Ago-2 as a miRNA delivery platform for the treatment of brain vascular diseases.

Indexed as

AnimalsArgonaute ProteinsBlotting, WesternBrainCells, CulturedEndothelium, VascularHumansIntracranial Arteriovenous MalformationsMaleMice, NudeMicroRNAsReal-Time Polymerase Chain ReactionAGO2 protein, humanArgonaute ProteinsMicroRNAsMIRN18A microRNA, humanangiogenesisArgonaute‐2arteriovenous malformationbrain endothelial cellsmiR‐18a

Identifiers

PMID24837588
PMCPMC4309089
OpenAlexW2145721530

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.