Evidence mapPaperPMID 41102495Full record

ArticleEMBO molecular medicine2025

Plasmodium falciparum impairs Ang-1 secretion by pericytes in a 3D brain microvessel model.

Rory K M Long, François Korbmacher, Paolo Ronchi, Hannah Fleckenstein, Martin Schorb, Waleed Mirza, Mireia Mallorquí, Ruth Aguilar, Gemma Moncunill, Yannick Schwab and 1 more

Abstract read
In one paragraph

Article in EMBO molecular medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
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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

11 authors.

Rory K M LongEuropean Molecular Biology Laboratory (EMBL) Barcelona, Barcelona, Spain.ORCID 0000-0003-0961-2786
François KorbmacherEuropean Molecular Biology Laboratory (EMBL) Barcelona, Barcelona, Spain.
Paolo RonchiElectron Microscopy Core Facility, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.ORCID 0000-0001-9010-533X
Hannah FleckensteinEuropean Molecular Biology Laboratory (EMBL) Barcelona, Barcelona, Spain.
Martin SchorbElectron Microscopy Core Facility, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
Waleed MirzaEuropean Molecular Biology Laboratory (EMBL) Barcelona, Barcelona, Spain.
Mireia MallorquíEuropean Molecular Biology Laboratory (EMBL) Barcelona, Barcelona, Spain.
Ruth AguilarBarcelona Institute for Global Health (ISGlobal), Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.
Gemma MoncunillBarcelona Institute for Global Health (ISGlobal), Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.ORCID 0000-0001-5105-9836
Yannick SchwabElectron Microscopy Core Facility, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
Maria BernabeuEuropean Molecular Biology Laboratory (EMBL) Barcelona, Barcelona, Spain. maria.bernabeu@embl.es.ORCID 0000-0001-7212-6209

Funding

EC | European Research Council (ERC) 948088EC | EU Social | European Social Fund Plus (ESF) RYC 2020-029886 I/ AEI/10.13039/501100011033EC | H2020 | PRIORITY 'Excellent science' | H2020 Marie Skłodowska-Curie Actions (MSCA) 101068552EC | H2020 | PRIORITY 'Excellent science' | H2020 Marie Skłodowska-Curie Actions (MSCA) 847543European Molecular Biology Laboratory (EMBL) NA
6 · The paper itself

Abstract

Disruption of the vascular protective angiopoietin-Tie axis is common in cerebral malaria (CM) patients, who display elevated angiopoietin-2 (Ang-2) and reduced angiopoietin-1 (Ang-1) blood concentrations. The role of pericytes in CM pathogenesis remains unexplored, despite being a major source of brain Ang-1 secretion and evidence of pericyte damage observed in CM postmortem samples. Here, we engineered a human 3D microfluidics-based brain microvessel model containing the minimal cellular components to replicate the angiopoietin-Tie axis, human primary brain microvascular endothelial cells, and pericytes. This model replicated pericyte vessel coverage and ultrastructural interactions present in the brain microvasculature. When exposed to P. falciparum-iRBC egress products, 3D brain microvessels presented decreased Ang-1 secretion, increased vascular permeability, and minor ultrastructural changes in pericyte morphology. Notably, P. falciparum-mediated barrier disruption was partially reversed after pre-treatment with recombinant Ang-1 and the Tie-2 activator, AKB-9778. Our approach suggests a novel mechanistic role of pericytes in CM pathogenesis and highlights the potential of therapeutics that target the angiopoietin-Tie axis to rapidly counteract vascular dysfunction caused by P. falciparum.

Indexed as

Angiopoietin-1BrainMicrovesselsPericytesPlasmodium falciparumEndothelial CellsHumansAngiopoietin-1ANGPT1 protein, human3D Brain Microvascular ModelsAKB-9778Angiopoietin–Tie AxisCerebral MalariaPericytes

Identifiers

PMID41102495
PMCPMC12603187

What Socratic holds

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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 Socratic graph.