Evidence map›Paper›PMID 39508403›Full record

ArticleJournal of extracellular vesicles2024

Hypoxia and TNF-alpha modulate extracellular vesicle release from human induced pluripotent stem cell-derived cardiomyocytes.

Margarida Viola, Maarten P Bebelman, Renee G C Maas, Willemijn S de Voogt, Frederik J Verweij, Cor S Seinen, Saskia C A de Jager, Pieter Vader, Dirk Michiel Pegtel, Joost Petrus Gerardus Sluijter

Abstract read
In one paragraph

Article in Journal of extracellular vesicles, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
–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

15 citing papers in PubMed, 1 synthesis or guideline pooled it.

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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.

Margarida ViolaDepartment of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.ORCID 0000-0001-6577-3520
Maarten P BebelmanDepartment of Pathology, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
Renee G C MaasDepartment of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Willemijn S de VoogtCDL Research, University Medical Center Utrecht, Utrecht, The Netherlands.
Frederik J VerweijDivision of Cell Biology, Neurobiology and Biophysics, Utrecht University, Utrecht, The Netherlands.ORCID 0000-0001-8879-1174
Cor S SeinenCDL Research, University Medical Center Utrecht, Utrecht, The Netherlands.
Saskia C A de JagerDepartment of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Pieter VaderDepartment of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.ORCID 0000-0002-7059-8920
Dirk Michiel PegtelDepartment of Pathology, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.ORCID 0000-0002-7357-4406
Joost Petrus Gerardus SluijterDepartment of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Funding

European Research Council Consolidator grant EVICARE (number 725229)
6 · The paper itself

Abstract

Extracellular vesicles (EVs) have emerged as important mediators of intercellular communication in the heart under homeostatic and pathological conditions, such as myocardial infarction (MI). However, the basic mechanisms driving cardiomyocyte-derived EV (CM-EV) production following stress are poorly understood. In this study, we generated human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) that express NanoLuc-tetraspanin reporters. These modified hiPSC-CMs allow for quantification of tetraspanin-positive CM-EV secretion from small numbers of cells without the need for time-consuming EV isolation techniques. We subjected these cells to a panel of small molecules to study their effect on CM-EV biogenesis and secretion under basal and stress-associated conditions. We observed that EV biogenesis is context-dependent in hiPSC-CMs. Nutrient starvation decreases CM-EV secretion while hypoxia increases the production of CM-EVs in a nSmase2-dependent manner. Moreover, the inflammatory cytokine TNF-α increased CM-EV secretion through a process involving NLRP3 inflammasome activation and mTOR signalling. Here, we detailed for the first time the regulatory mechanisms of EV biogenesis in hiPSC-CMs upon MI-associated stressors.

Indexed as

Cell HypoxiaExtracellular VesiclesInduced Pluripotent Stem CellsMyocytes, CardiacTumor Necrosis Factor-alphaHumansInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinSignal TransductionInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinTumor Necrosis Factor-alphacardiomyocytesEV biogenesisextracellular vesiclesmyocardial infarctionNanoLuc

Identifiers

PMID39508403
PMCPMC11541862

What OpenQuestion holds

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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.