ArticleDevelopmental biology2013
Epicardial HIF signaling regulates vascular precursor cell invasion into the myocardium.
Article in Developmental biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 48 citations in OpenAlex.
- 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
- Article
- Epicardium-myocardium crosstalk orchestrates heart development.Frontiers in cell and developmental biology · 2025Review
- The Wilms' Tumor Suppressor WT1 in Cardiomyocytes: Implications for Cardiac Homeostasis and Repair.Cells · 2024Review
- Mef2c- and Nkx2-5-Divergent Transcriptional Regulation of Chick WT1_76127 and Mouse Gm14014 lncRNAs and Their Implication in Epicardial Cell Migration.International journal of molecular sciences · 2024Article
- Epicardial EMT and cardiac repair: an update.Stem cell research & therapy · 2024Review
- The Neural Progenitor Cell-Associated Transcription Factor FoxG1 Regulates Cardiac Epicardial Cell Proliferation.Stem cells international · 2024Article
- Novel Insights into the Molecular Mechanisms Governing Embryonic Epicardium Formation.Journal of cardiovascular development and disease · 2023Review
- Maternal nicotine exposure induces congenital heart defects in the offspring of mice.Journal of cellular and molecular medicine · 2022Article
- HIF in the heart: development, metabolism, ischemia, and atherosclerosis.The Journal of clinical investigation · 2021Review
- Epicardial Contribution to the Developing and Injured Heart: Exploring the Cellular Composition of the Epicardium.Frontiers in cardiovascular medicine · 2021Review
- Coronary Revascularization During Heart Regeneration Is Regulated by Epicardial and Endocardial Cues and Forms a Scaffold for Cardiomyocyte Repopulation.Developmental cell · 2019Article
- Maternal voluntary exercise mitigates oxidative stress and incidence of congenital heart defects in pre-gestational diabetes.Journal of cellular and molecular medicine · 2019Article
- Recent insights on the role and regulation of retinoic acid signaling during epicardial development.Genesis (New York, N.Y. : 2000) · 2019Review
- The therapeutic potential of targeting the endothelial-to-mesenchymal transition.Angiogenesis · 2019Review
- Alterations in retinoic acid signaling affect the development of the mouse coronary vasculature.Developmental dynamics : an official publication of the American Association of Anatomists · 2018Article
- Hypoxia Supports Epicardial Cell Differentiation in Vascular Smooth Muscle Cells through the Activation of the TGFβ Pathway.Journal of cardiovascular development and disease · 2018Article
- Hypoxia induced the differentiation of Tbx18-positive epicardial cells to CoSMCs.Scientific reports · 2016Article
- Epicardium-Derived Cells Formed After Myocardial Injury Display Phagocytic Activity Permitting In Vivo Labeling and Tracking.Stem cells translational medicine · 2016Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
During cardiogenesis, a subset of epicardial cells undergoes epithelial-mesenchymal-transition (EMT) and the resulting epicardial-derived cells (EPDCs) contribute to the formation of coronary vessels. Our previous data showed hypoxia inducible factor-1α (HIF-1α) expression at specific sites within the epicardium and support a link between hypoxia inducible factors (HIFs) and the patterning of coronary vasculogenesis. To better understand the autocrine role of HIFs in the epicardium, we transduced adenovirus mediated expression of constitutively active HIF-1α (AdcaHIF1α) into the embryonic avian epicardium where the vascular precursors reside. We found that introducing caHIF1α into the epicardial mesothelium prevented EPDCs from proper migration into the myocardium. In vitro collagen gel assays and ex vivo organ culture data further confirmed that infection with AdcaHIF1α impaired the ability of EPDCs to invade. However, the proficiency of epicardial cells to undergo EMT was enhanced while the movement of EPDCs within the sub-epicardium and their differentiation into smooth muscle cells were not disrupted by caHIF1α. We also showed that the transcript level of Flt-1 (VEGFR1), which can act as a VEGF signaling inhibitor, increased several fold after introducing caHIF1α into epicardial cells. Blocking the activation of the VEGF pathway in epicardial cells recapitulated the inhibition of EPDC invasion. These results suggest that caHIF1α mediated up-regulation of Flt-1, which blocks the activation of the VEGF pathway, is responsible for the inhibition of EPDC myocardial migration. In conclusion, our studies demonstrate that HIF signaling potentially regulates the degree of epicardial EMT and the extent of EPDC migration into the myocardium, both of which are likely critical in patterning the coronary vasculature during early cardiac vasculogenesis. These signals could explain why the larger coronaries appear and remain on the epicardial surface.
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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.