Evidence map›Paper›PMID 32151395›Full record

ArticleAtherosclerosis2020

The identification and function of a Netrin-1 mutation in a pedigree with premature atherosclerosis.

Caroline S Bruikman, Dianne Vreeken, Huayu Zhang, Marit J van Gils, Jorge Peter, Anton Jan van Zonneveld, G Kees Hovingh, Janine M van Gils

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Atherosclerosis, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.2field-weighted citation impact, top 24% 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

13 citing papers in PubMed, 14 citations in OpenAlex.

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  8. Netrin-1: A Modulator of Macrophage Driven Acute and Chronic Inflammation.International journal of molecular sciences · 2021
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Caroline S BruikmanAmsterdam UMC, University of Amsterdam, Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Meibergdreef 9, Amsterdam, the Netherlands.
Dianne VreekenLeiden University Medical Center, Department of Internal Medicine (Nephrology), Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden, the Netherlands.
Huayu ZhangLeiden University Medical Center, Department of Internal Medicine (Nephrology), Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden, the Netherlands.
Marit J van GilsAmsterdam UMC, University of Amsterdam, Department of Medical Microbiology, Meibergdreef 9, Amsterdam, the Netherlands.
Jorge PeterAmsterdam UMC, University of Amsterdam, Department of Experimental Vascular Medicine, Meibergdreef 9, Amsterdam, the Netherlands.
Anton Jan van ZonneveldLeiden University Medical Center, Department of Internal Medicine (Nephrology), Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden, the Netherlands.
G Kees HovinghAmsterdam UMC, University of Amsterdam, Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Meibergdreef 9, Amsterdam, the Netherlands.
Janine M van GilsLeiden University Medical Center, Department of Internal Medicine (Nephrology), Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden, the Netherlands. Electronic address: j.m.van_gils@lumc.nl.
Leiden University Medical Center · NLAmsterdam University Medical Centers · NLUniversity of Amsterdam · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

aimsNeuroimmune guidance cues have been shown to play a role in atherosclerosis, but their exact role in human pathophysiology is largely unknown. In the current study, we investigated the role of a c.1769G > T variant in Netrin-1 in (premature) atherosclerosis.

methodsTo determine the effect of the genetic variation, purified Netrin-1, either wild type (wtNetrin-1) or the patient observed variation (mutNetrin-1), was used for migration, adhesion, endothelial barrier function and bindings assays. Expression of adhesion molecules and transcription proteins was analyzed by RT-PCR, Western blot or ELISA. To further delineate how mutNetrin-1 mediates its effect on cell migration, lenti-viral knockdown of UNC5B or DCC was used.

resultsBindings assays revealed a decreased binding capacity of mutNetrin-1 to the receptors UNC5B, DCC and β3-integrin and an increased binding capacity to neogenin, heparin and heparan sulfate compared to wtNetrin-1. Exposure of endothelial cells to mutNetrin-1 resulted in enhanced monocyte adhesion and expression of IL-6, CCL2 and ICAM-1 compared to wtNetrin-1. In addition, mutNetrin-1 lacks the inhibitory effect on the NF-κB pathway that is observed for wtNetrin-1. Moreover, the presence of mutNetrin-1 diminished migration of macrophages and smooth muscle cells. Importantly, UNC5B or DCC specific knockdown showed that mutNetrin-1 is unable to act through DCC resulting in enhanced inhibition of migration.

conclusionsOur data demonstrates that mutNetrin-1 fails to exert anti-inflammatory effects on endothelial cells and more strongly blocks macrophage migration compared to wtNetrin-1, suggesting that the carriers of this genetic molecular variant may well be at risk for premature atherosclerosis.

Indexed as

AtherosclerosisDCC ReceptorEndothelial CellsHumansMutationNetrin-1Netrin ReceptorsPedigreeReceptors, Cell SurfaceTumor Suppressor ProteinsDCC protein, humanDCC ReceptorNetrin-1Netrin ReceptorsReceptors, Cell SurfaceTumor Suppressor ProteinsUNC5B protein, humanAtherosclerosisEndothelial functionInflammationMacrophagesMonocytesNetrin-1

Identifiers

PMID32151395
OpenAlexW3009448427

What OpenQuestion holds

Textmetadata
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.