Abstract
The epicardium is an epithelial monolayer that plays a central role in heart development and the myocardial response to injury. Recent developments in our understanding of epicardial cell biology have revealed this layer to be a dynamic participant in fundamental processes underlying the development of the embryonic ventricles, the coronary vasculature, and the cardiac valves. Likewise, recent data have identified the epicardium as an important contributor to reparative and regenerative processes in the injured myocardium. These essential functions of the epicardium rely on both non-cell autonomous and cell-autonomous mechanisms, with the latter featuring the process of epicardial Epithelial-to-Mesenchymal Transition (EMT). This review will focus on the induction and regulation of epicardial EMT, as it pertains to both cardiogenesis and the response of the myocardium to injury.
Highlights
The epicardium consists of an epithelial monolayer located on the outermost surface of the heart, serving as a boundary between the underlying myocardium and the pericardial cavity.Early developmental biologists regarded the epicardium as an inert barrier, and the functional importance of epicardial cells in both heart development and cardiac disease was largely neglected throughout much of the late 19th and early 20th centuries
Lineage tracing experiments and gene expression analysis have demonstrated that these epicardial derived cells (EPDCs) give rise to fibroblast-like cells and myofibroblasts that likely contribute to fibrosis, with no substantiated evidence suggesting that epicardial Epithelial-to-Mesenchymal Transition (EMT) serves to replenish the cardiomyocyte population within the infarct zone [11,82]
Our view of the epicardium as a myocardial-derived barrier has been supplanted by an understanding of the epicardium as a highly functional epithelial monolayer that actively participates in heart development and the myocardial response to ischemic injury
Summary
The epicardium consists of an epithelial monolayer located on the outermost surface of the heart, serving as a boundary between the underlying myocardium and the pericardial cavity. Additional work by Acharya and colleagues, as well as Kikuchi et al, demonstrated that PEO progenitor cells expessing Tcf preferentially give rise to cells of the cardiac fibroblast lineage [10,11] These data support a model in which genetic determination of fate specification occurs prior to epicardial EMT, and perhaps prior to the assembly of progenitor cells within the PEO. After epicardial investment has begun, a subset of epicardial cells overlying the AV groove separate from the epicardial monolayer and form the sub-epicardial mesenchyme These cells, termed Epicardial Derived Cell (EPDCs), initially express both epithelial and mesenchymal markers, and represent a dedifferentiation of epithelial cells to an intermediary cell with enhanced developmental plasticity and intriguing multipotency [12]
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