Evidence map›Paper›PMID 41271808›Full record

ArticleScientific reports2025

Revealing the complexity of the epicardial secretome.

Cláudia C Oliveira, José Córdoba, John R Pearson, Elizabeth Guruceaga, Ernesto Marín-Sedeño, María López-Moreno, Juan Antonio Guadix, Melissa García-Caballero, José M Pérez-Pomares, Adrián Ruiz-Villalba

Abstract read
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
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.

Cláudia C OliveiraDepartment of Animal Biology, Faculty of Sciences, University of Málaga, Campus de Teatinos s/n, 29080, Málaga, Spain.
José CórdobaDepartment of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, Campus de Teatinos s/n, 29080, Málaga, Spain.
John R PearsonLeica Microsystems, Barcelona, Spain.
Elizabeth GuruceagaBioinformatics Platform, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
Ernesto Marín-SedeñoDepartment of Animal Biology, Faculty of Sciences, University of Málaga, Campus de Teatinos s/n, 29080, Málaga, Spain.
María López-MorenoDepartment of Animal Biology, Faculty of Sciences, University of Málaga, Campus de Teatinos s/n, 29080, Málaga, Spain.
Juan Antonio GuadixDepartment of Animal Biology, Faculty of Sciences, University of Málaga, Campus de Teatinos s/n, 29080, Málaga, Spain.
Melissa García-CaballeroInstituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA Plataforma BIONAND), Málaga, Spain.
José M Pérez-PomaresDepartment of Animal Biology, Faculty of Sciences, University of Málaga, Campus de Teatinos s/n, 29080, Málaga, Spain. jmperezp@uma.es.
Adrián Ruiz-VillalbaDepartment of Animal Biology, Faculty of Sciences, University of Málaga, Campus de Teatinos s/n, 29080, Málaga, Spain. adruiz@uma.es.

Funding

Agencia Estatal de Investigación RYC21-034611-IFundación Científica Asociación Española Contra el Cáncer LABAE211691- GARCHORIZON EUROPE Marie Sklodowska-Curie Actions NanoMed PhD - 713721, MSCA-COFUND-2015-DPInstituto de Salud Carlos III PI21/00653Ministerio de Ciencia e Innovación PID2020-119430RJ-I00Ministerio de Ciencia e Innovación RTI2018-095410-BI00Ministerio de Universidades FPU18-05219Sociedad Española de Cardiología SEC/FEC-INV-BAS 22/016
6 · The paper itself

Abstract

The epicardium, an epithelial layer covering the heart, plays pivotal roles in embryonic heart development and responses to adult cardiac damage. Epicardial-secreted molecular agents are known to be involved in the regulation of these phenomena, but how this regulation occurs is poorly understood. In this study, we have investigated extracellular vesicle (EV) and extracellular matrix (ECM) components of the epicardial secretome using a continuous mouse embryonic epicardial-derived cell (EPIC) line. Epicardial-derived EVs were isolated using differential ultracentrifugation from EPIC cultured at 1% (EVs-H1%), 5% (EVs-H5%), and 21% oxygen (EVs-N). EVs protein content was determined by tandem mass tag (TMT) proteomic analysis. The results showed that epicardial-derived EVs cargo is sensitive to the oxygen level of parenteral cells, increasing their content on glycolytic proteins as oxygen level decreases. Moreover, hypoxic-derived EVs were found to both increase EPIC proliferation and affect the metabolism of Human Umbilical Vein Endothelial Cells (HUVECs). On the other hand, epicardial-derived extracellular matrix (EPIC-ECM) was characterized by submitting decellularized EPIC to shotgun proteomics and comparing it to decellularized perinatal hearts and Matrigel®. We found that EPIC-ECM composition closely resembles that of embryonic cardiac tissue. Although the structural and basement membrane-associated proteins of EPIC-ECM were similar to those found in Matrigel®, EPIC-ECM exhibited higher protein diversity and was a more potent inducer of HUVEC proliferation. This work represents the first comprehensive and systematic proteomic analysis of two important components of the epicardial-derived secretome. Our experiments reveal that the epicardium responds to hypoxia by secreting EVs capable of modifying the metabolic responses of surrounding cells. Furthermore, EPIC-ECM promotes endothelial cell proliferation. These findings demonstrate the significant signaling abilities of the epicardial secretome and its potential contribution to cardiac development, both consistent with reports of endothelial responses following cardiac ischemic damage.

Indexed as

Extracellular VesiclesPericardiumSecretomeAnimalsCell LineCell ProliferationExtracellular MatrixHumansHuman Umbilical Vein Endothelial CellsMiceOxygenProteomeProteomicsOxygenProteome

Identifiers

PMID41271808
PMCPMC12639070

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Registered trials

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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.