The epicardium plays a key role during cardiac development, homeostasis and repair, and has thus emerged as a potential target in the treatment of cardiovascular disease. However, therapeutically manipulating the epicardium and epicardium-derived cells (EPDCs) requires insights into their developmental origin and the mechanisms driving their activation, recruitment and contribution to both the embryonic and adult injured heart. In recent years, studies of various model systems have provided us with a deeper understanding of the microenvironment in which EPDCs reside and emerge into, of the crosstalk between the multitude of cardiovascular cell types that influence the epicardium, and of the genetic programmes that orchestrate epicardial cell behaviour. Here, we review these discoveries and discuss how technological advances could further enhance our knowledge of epicardium-based repair mechanisms and ultimately influence potential therapeutic outcomes in cardiovascular regenerative medicine.
Isolation, characterization, and expression of the murine Wilms' tumor gene (WT1) during kidney development.
Development of the cardiac coronary vascular endothelium, studied with antiendothelial antibodies, in chicken-quail chimeras
Pericardial mesoderm generates a population of coronary smooth muscle cells migrating into the heart along with ingrowth of the epicardial organ
Contribution of the primitive epicardium to the subepicardial mesenchyme in hamster and chick embryos
Common epicardial origin of coronary vascular smooth muscle, perivascular fibroblasts, and intermyocardial fibroblasts in the avian heart
Cloning of capsulin, a basic helix-loop-helix factor expressed in progenitor cells of the pericardium and the coronary arteries
The origin of the subepicardial mesenchyme in the avian embryo: an immunohistochemical and quail-chick chimera study
epicardin: A novel basic helix-loop-helix transcription factor gene expressed in epicardium, branchial arch myoblasts, and mesenchyme of developing lung, gut, kidney, and gonads
Does the subepicardial mesenchyme contribute myocardioblasts to the myocardium of the chick embryo heart? A quail-chick chimera study tracing the fate of the epicardial primordium
Positive and negative regulation of epicardial-mesenchymal transformation during avian heart development
Dual functions of [alpha]4[beta]1 integrin in epicardial development: initial migration and long-term attachment
Prolonged fluid shear stress induces a distinct set of endothelial cell genes, most specifically lung Krüppel-like factor (KLF2).
Epicardial-like cells on the distal arterial end of the cardiac outflow tract do not derive from the proepicardium but are derivatives of the cephalic pericardium
Oxygen-regulated expression of the Wilms' tumor suppressor Wt1 involves hypoxia-inducible factor-1 (HIF-1)
Expression patterns of Tgfbeta1-3 associate with myocardialisation of the outflow tract and the development of the epicardium and the fibrous heart skeleton
Evidence for an extracellular matrix bridge guiding proepicardial cell migration to the myocardium of chick embryos
Epicardial retinoid X receptor alpha is required for myocardial growth and coronary artery formation
In vivo and in vitro analysis of the vasculogenic potential of avian proepicardial and epicardial cells
Formation of the venous pole of the heart from an Nkx2-5-negative precursor population requires Tbx18
BMP and FGF regulate the differentiation of multipotential pericardial mesoderm into the myocardial or epicardial lineage
Epicardial cells of human adults can undergo an epithelial-to-mesenchymal transition and obtain characteristics of smooth muscle cells in vitro
A dynamic epicardial injury response supports progenitor cell activity during zebrafish heart regeneration
Morphological and molecular left-right asymmetries in the development of the proepicardium: a comparative analysis on mouse and chick embryos
The grateful dead: damage-associated molecular pattern molecules and reduction/oxidation regulate immunity
Regulated addition of new myocardial and epicardial cells fosters homeostatic cardiac growth and maintenance in adult zebrafish.
Differential growth and multicellular villi direct proepicardial translocation to the developing mouse heart
Epicardial development in lamprey supports an evolutionary origin of the vertebrate epicardium from an ancestral pronephric external glomerulus
Prokineticin receptor-1 induces neovascularization and epicardial-derived progenitor cell differentiation
Mesothelial mobilization in the developing lung and heart differs in timing, quantity, and pathway dependency
Novel technique for the simultaneous isolation of cardiac fibroblasts and epicardial stromal cells from the infarcted murine heart
Single cell transcriptomics identifies a signaling network coordinating endoderm and mesoderm diversification during foregut organogenesis.
Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart.
Regenerative potential of epicardium-derived extracellular vesicles mediated by conserved miRNA transfer.
Single-Cell RNA Sequencing Uncovers Paracrine Functions of the Epicardial-Derived Cells in Arrhythmogenic Cardiomyopathy.
The extracellular matrix protein agrin is essential for epicardial epithelial-to-mesenchymal transition during heart development.
Deletion of a Hand1 lncRNA-Containing Septum Transversum Enhancer Alters lncRNA Expression but Is Not Required for Hand1 Expression.
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