ArticleJournal of cardiovascular development and disease2018
Hypoxia Supports Epicardial Cell Differentiation in Vascular Smooth Muscle Cells through the Activation of the TGFβ Pathway.
Article in Journal of cardiovascular development and disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Hypoxia-activated scleraxis a mediates epicardial progenitor differentiation into a unique cardiac perivascular cell type.Nature communications · 2026Article
- Hypoxia-mediated epicardial signaling coordinates coronary angiogenesis and myocardial expansion during zebrafish ventricle maturation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Spiny Mice Show a Profibrotic Epicardial Mesothelial Response to Hypoxic Injury Comparable to C57BL/6 Mice.Biomolecules · 2026Article
- Attenuation of epicardial activation and myofibroblast abundance via the Fbln2-Nupr1b axis stimulates cardiac regeneration in zebrafish.Nature cardiovascular research · 2026Article
- Revealing the complexity of the epicardial secretome.Scientific reports · 2025Article
- Article
- Epicardium-myocardium crosstalk orchestrates heart development.Frontiers in cell and developmental biology · 2025Review
- Epicardial EMT and cardiac repair: an update.Stem cell research & therapy · 2024Review
- Epicardioid single-cell genomics uncovers principles of human epicardium biology in heart development and disease.Nature biotechnology · 2023Article
- The TFEB-TGIF1 axis regulates EMT in mouse epicardial cells.Nature communications · 2022Article
- Hypoxia promotes a perinatal-like progenitor state in the adult murine epicardium.Scientific reports · 2022Article
- Review
- Bioengineering strategies to control epithelial-to-mesenchymal transition for studies of cardiac development and disease.APL bioengineering · 2021Review
- Mechanisms of Hypoxia-Induced Pulmonary Arterial Stiffening in Mice Revealed by a Functional Genetics Assay of Structural, Functional, and Transcriptomic Data.Frontiers in physiology · 2021Article
- Epicardial TGFβ and BMP Signaling in Cardiac Regeneration: What Lesson Can We Learn from the Developing Heart?Biomolecules · 2020Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Epicardium-derived cells (EPDCs) are an important pool of multipotent cardiovascular progenitor cells. Through epithelial-to-mesenchymal-transition (EMT), EPDCs invade the subepicardium and myocardium and further differentiate into several cell types required for coronary vessel formation. We previously showed that epicardial hypoxia inducible factor (HIF) signaling mediates the invasion of vascular precursor cells critical for patterning the coronary vasculature. Here, we examine the regulatory role of hypoxia (1% oxygen) on EPDC differentiation into vascular smooth muscle cells (VSMCs).
resultsHypoxia stimulates EMT and enhances expression of several VSMC markers in mouse epicardial cell cultures. This stimulation is specifically blocked by inhibiting transforming growth factor-beta (TGFβ) receptor I. Further analyses indicated that hypoxia increases the expression level of TGFβ-1 ligand and phosphorylation of TGFβ receptor II, suggesting an indispensable role of the TGFβ pathway in hypoxia-stimulated VSMC differentiation. We further demonstrate that the non-canonical RhoA/Rho kinase (ROCK) pathway acts as the main downstream effector of TGFβ to modulate hypoxia’s effect on VSMC differentiation.
conclusionOur results reveal a novel role of epicardial HIF in mediating coronary vasculogenesis by promoting their differentiation into VSMCs through noncanonical TGFβ signaling. These data elucidate that patterning of the coronary vasculature is influenced by epicardial hypoxic signals.
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Registered trials
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.