Evidence map›Paper›PMID 34853722›Full record

ArticleMolecular therapy. Nucleic acids2021

Inhibition of microRNA-494-3p activates Wnt signaling and reduces proinflammatory macrophage polarization in atherosclerosis.

Eva van Ingen, Amanda C Foks, Tamar Woudenberg, M Leontien van der Bent, Alwin de Jong, Philipp J Hohensinner, Johann Wojta, Ilze Bot, Paul H A Quax, Anne Yaël Nossent

Open access · goldAbstract read
In one paragraph

Article in Molecular therapy. Nucleic acids, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 14% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.

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  5. Vitamin D Reprograms Non-Coding RNA Networks to Block Zika Virus in Human Macrophages.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026
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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

10 authors at 5 institutions in 2 countries.

Eva van IngenDepartment of Surgery, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
Amanda C FoksDivision of BioTherapeutics, LACDR, Leiden University, 2333 CC Leiden, The Netherlands.
Tamar WoudenbergDepartment of Surgery, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
M Leontien van der BentDepartment of Surgery, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
Alwin de JongDepartment of Surgery, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
Philipp J HohensinnerDepartment of Internal Medicine II, Medical, University of Vienna, 1090 Vienna, Austria.
Johann WojtaDepartment of Internal Medicine II, Medical, University of Vienna, 1090 Vienna, Austria.
Ilze BotDivision of BioTherapeutics, LACDR, Leiden University, 2333 CC Leiden, The Netherlands.
Paul H A QuaxDepartment of Surgery, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
Anne Yaël NossentDepartment of Surgery, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
Leiden University Medical Center · NLLeiden University · NLLudwig Boltzmann Institute for Cancer Research · ATMedical University of Vienna · ATUniversity of Vienna · AT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We have previously shown that treatment with third-generation antisense oligonucleotides against miR-494-3p (3GA-494) reduces atherosclerotic plaque progression and stabilizes lesions, both in early and established plaques, with reduced macrophage content in established plaques. Within the plaque, different subtypes of macrophages are present. Here, we aimed to investigate whether miR-494-3p directly influences macrophage polarization and activation. Human macrophages were polarized into either proinflammatory M1 or anti-inflammatory M2 macrophages and simultaneously treated with 3GA-494 or a control antisense (3GA-ctrl). We show that 3GA-494 treatment inhibited miR-494-3p in M1 macrophages and dampened M1 polarization, while in M2 macrophages miR-494-3p expression was induced and M2 polarization enhanced. The proinflammatory marker CCR2 was reduced in 3GA-494-treated atherosclerosis-prone mice. Pathway enrichment analysis predicted an overlap between miR-494-3p target genes in macrophage polarization and Wnt signaling. We demonstrate that miR-494-3p regulates expression levels of multiple Wnt signaling components, such as LRP6 and TBL1X. Wnt signaling appears activated upon treatment with 3GA-494, both in cultured M1 macrophages and in plaques of hypercholesterolemic mice. Taken together, 3GA-494 treatment dampened M1 polarization, at least in part via activated Wnt signaling, while M2 polarization was enhanced, which is both favorable in reducing atherosclerotic plaque formation and increasing plaque stability.

Indexed as

14q32 locusantisense oligonucleotidesatherosclerosiscardiovascular diseaseDLK1-DIO3 locusinflammationmacrophage polarizationmicroRNAmicroRNA-494-3pWnt signaling

Identifiers

PMID34853722
PMCPMC8607137
OpenAlexW3214152223

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.