Signaling During Epicardium and Coronary Vessel Development

Abstract

Abstract:The epicardium, the tissue layer covering the cardiac muscle (myocardium), develops from the proepicardium, a mass of coelomic progenitors located at the venous pole of the embryonic heart. Proepicardium cells attach to and spread over the myocardium to form the primitive epicardial epithelium. The epicardium subsequently undergoes an epithelial-to-mesenchymal transition to give rise to a population of epicardiumderived cells, which in turn invade the heart and progressively differentiate into various cell types, including cells of coronary blood vessels and cardiac interstitial cells. Epicardial cells and epicardium-derived cells signal to the adjacent cardiac muscle in a paracrine fashion, promoting its proliferation and expansion. Recently, high expectations have been raised about the epicardium as a candidate source of cells for the repair of the damaged heart. Because of its developmental importance and therapeutic potential, current research on this topic focuses on the complex signals that control epicardial biology. This review describes the signaling pathways involved in the different stages of epicardial development and discusses the potential of epicardial signals as targets for the development of therapies to repair the diseased heart. (Circ Res. 2011;109:1429-1442.)

Preotic neural crest cells contribute to coronary artery smooth muscle involving endothelin signalling

“…Orthotopic grafting of quail proepicardial tissues into chick embryos revealed that QCPNnegative SMCs in the septal branch, as well as in arteries in the free wall, are predominantly of proepicardial origin (Supplementary Fig. S13), as reported previously [11][12][13] .…”

“…Coronary arteries are generally accepted to form by ingrowth of angiogenic precursors into the aorta [8][9][10] , with the integration of migrating proepicardial mesenchyme as the main source of smooth muscle cells (SMCs) [11][12][13] . On the other hand, quail-chick chimera experiments have shown that the cardiac NC does not differentiate into coronary SMCs, although ganglia of NC origin are associated with the proximal portion of coronary arteries 10,14 .…”

Extracardiac septum transversum/proepicardial endothelial cells pattern embryonic coronary arterio–venous connections

“…To understand the morphogenesis of the coronary vascular system fully, we need to uncover the molecular and cellular mechanisms that integrate different endothelial compartments (i.e., the embryonic arterial and venous coronary vasculature) into a single, continuous vascular bed and to identify the origin of coronary endothelial progenitors (1). In this regard, Katz and collaborators (13) have proven that the PE comprises several cell compartments (identified by either Scleraxis or Semaphorin3D gene expression) that contribute differentially to CoE.…”

“…G2-Gata4-driven reporter expression first is confined to the epicardium and its mesenchymal derivatives (1,(20)(21)(22) and then expands to the CoE.…”

“…coronary endothelium | septum transversum | proepicardium | Gata4 | Wt1 T he coronary vascular system, whose function is necessary to sustain late embryonic and postnatal cardiac function, is formed by a complex network of blood vessels, including arteries, arterioles, capillaries, venules, and veins (1). Recent reports indicate that various sources of endothelial cells contribute to the mammalian embryonic coronary system (2-4).…”