More than Just a Simple Cardiac Envelope; Cellular Contributions of the Epicardium
Open accessAbstract
The adult pumping heart is formed by distinct tissue layers. From inside to outside, the heart is composed by an internal endothelial layer, dubbed the endocardium, a thick myocardial component which supports the pumping capacity of the heart and exteriorly covered by a thin mesothelial layer named the epicardium. Cardiac insults such as coronary artery obstruction lead to ischemia and thus to an irreversible damage of the myocardial layer, provoking in many cases heart failure and death. Thus, searching for new pathways to regenerate the myocardium is an urgent biomedical need. Interestingly, the capacity of heart regeneration is present in other species, ranging from fishes to neonatal mammals. In this context, several lines of evidences demonstrated a key regulatory role for the epicardial layer. In this manuscript, we provide a state-of-the-art review on the developmental process leading to the formation of the epicardium, the distinct pathways controlling epicardial precursor cell specification and determination and current evidences on the regenerative potential of the epicardium to heal the injured heart.
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EAT is a major source of mesenchymal stem cells that can provide regeneration and repair of injured myocardium.
“Additionally, EAT is a major source of mesenchymal stem cells that, transiting through the shared microcirculation, can provide the regeneration and repair of injured myocardium [48,49].”
From Dysregulated epicardial adipose tissue as a risk factor and potential therapeutic target of heart failure with preserved ejection fraction in diabetes (2022) · cites this paper as [49]
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In Vivo and In Vitro Cartilage Differentiation from Embryonic Epicardial Progenitor Cells
Palmquist‐Gomes, P., Marín‐Sedeño, E., Ruiz‐Villalba, A., Rico-Llanos, G., Pérez-Pomares, J. M., & Guadix, J. A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23073614 · Cited by 4 · see citing works
Can EAT be an INOCA goalkeeper
Tong, S., Shuwen, Z., Hengbin, W., & Zeng, M. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1028429 · Cited by 3 · see citing works
Analysis of wt1a reporter line expression levels during proepicardium formation in the zebrafish.
Andrés‐Delgado, L., Galardi‐Castilla, M., Mercader, N., & Santamarı́a, L. (2020) · PubMed · doi:10.14670/hh-18-238 · Cited by 3 · see citing works
Caño-Carrillo, S., García‐Padilla, C., Aránega, A. E., Lozano-Velasco, E., & Franco, D. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252312904 · Cited by 2 · see citing works
Self-citationCardiac Development: A Glimpse on Its Translational Contributions
Franco, D., García‐Padilla, C., Dominguez, J. N., Lozano-Velasco, E., & Aránega, A. E. (2021) · Hearts · doi:10.3390/hearts2010008 · Cited by 3 · see citing works
Self-citationActomyosin dynamics, Bmp and Notch signaling pathways drive apical extrusion of proepicardial cellsPreprint
Andrés‐Delgado, L., Ernst, A., Galardi‐Castilla, M., Bazaga, D., Peralta, M., Münch, J., González‐Rosa, J. M., Tessadori, F., Bakkers, J., de la Pompa, J. L., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/332593 · Cited by 2 · see citing works
Castillo-Casas, J. M., Dueñas, Á., Hernández‐Torres, F., Carmona, R., Muñoz‐Chápuli, R., Dopazo, A., Álvarez, R., Vázquez, E., Aránega, A. E., Franco, D., et al. (2025) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-025-05735-4 · Cited by 2 · see citing works
Self-citationHealing the Broken Hearts: A Glimpse on Next Generation Therapeutics
Franco, D., & Lozano-Velasco, E. (2022) · Hearts · doi:10.3390/hearts3040013 · Cited by 1 · see citing works
Self-citationThe Genetic Paradigm of WT1 Gene in Heart Development and Cardiac Repair
Liu, X., Chen, M., Deng, X., & Ding, Z. (2018) · Translational bioinformatics · doi:10.1007/978-981-13-1429-2_6
- Authors
- Dueñas, A., Aranega, A. E., & Franco, D.
- Affiliations
- Universidad de Jaén (ES)
- Corresponding author
- Franco, Diego
- ORCID
- Franco, Diego
- Venue
- Frontiers in Cell and Developmental Biology
- Publisher
- Frontiers Media SA
- Published
- 2017-05-01
- Volume
- 5
- Pages
- 44-44
- ISSN
- 2296-634X (ISSN-L)
- PMC
- PMC5410615
- OpenAlex
- W2610768059
- Cited by
- 25
- References
- 172
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 2 · 2022: 6 · 2021: 2 · 2020: 4 · 2019: 2 · 2018: 7
- FWCI
- 0.33
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Cell and Developmental Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Ministerio de Economía y Competitividad (BFU2015-67131P)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- epicardium, cardiac regeneration, myocardial injury, heart failure, coronary artery obstruction, mesothelium, endocardium, myocardium
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