Epicardial–Myocardial Signaling Directing Coronary Vasculogenesis

Olivey, Harold E.; Svensson, E. C.

doi:10.1161/circresaha.109.209197

Cited by 137 publications

(144 citation statements)

References 123 publications

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“…28 Our study provides data on the expression and function of Notch elements throughout the development of the epicardial lineage. Our results demonstrate that Notch ligands (Delta1, Delta4 and Jagged1) and receptors (Notch2-4, but not Notch1) are present and/or active in the developing epicardial progenitor (proepicardium).…”

Section: Del Monte Et Al Notch Expression and Function In The Epicardiummentioning

confidence: 97%

Differential Notch Signaling in the Epicardium Is Required for Cardiac Inflow Development and Coronary Vessel Morphogenesis

Monte

Casanova

Guadix

et al. 2011

Circulation Research

152

134

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Rationale:The proepicardium is a transient structure comprising epicardial progenitor cells located at the posterior limit of the embryonic cardiac inflow. A network of signals regulates proepicardial cell fate and defines myocardial and nonmyocardial domains at the venous pole of the heart. During cardiac development, epicardial-derived cells also contribute to coronary vessel morphogenesis.Objective: To study Notch function during proepicardium development and coronary vessel formation in the mouse. Methods and Results:Using in situ hybridization, RT-PCR, and immunohistochemistry, we find that Notch pathway elements are differentially activated throughout the proepicardial-epicardial-coronary transition. Analysis of RBPJk-targeted embryos indicates that Notch ablation causes ectopic procardiogenic signaling in the proepicardium that in turn promotes myocardial differentiation in adjacent mesodermal progenitors, resulting in a premature muscularization of the sinus venosus horns. Epicardium-specific Notch1 ablation using a Wt1-Cre driver line disrupts coronary artery differentiation, reduces myocardium wall thickness and myocyte proliferation, and reduces Raldh2 expression. Ectopic Notch1 activation disrupts epicardium development and causes thinning of ventricular walls. T he early vertebrate heart consists of 2 tissue layers, the outer myocardium and the inner endocardium. At embryonic day (E)9.5 in mice, a third tissue, the epicardium, migrates to envelop the outer surface of the myocardium, actively participating in coronary vessels (CVs) morphogenesis and compact ventricular myocardium growth. 1 Epicardial progenitors are found in the proepicardium, a grape-like structure with characteristic protrusions (proepicardial villi). The proepicardium arises by E9.0 through local proliferation of the coelomic epithelium covering the septum transversum at the posterior limit (venous pole) of the heart. 2 The mesodermal progenitors underneath the proepicardium are often referred to as "posterior pericardial mesoderm," 3 a term that refers to topology rather than an embryological relation to the pericardial membranes. The venous pole of the heart provides the developing heart with myocardium, 4 a process that in the mouse finishes with the muscularization of the sinus horns. 5 The completion of the primitive epicardial epithelium covering the myocardium is followed by the appearance of the subepicardium, 1 an abundant extracellular matrix separating epicardium and myocardium. Concomitantly, the epicardium undergoes an epithelial-tomesenchymal transition (EMT) and populates the subepicardium with mesenchymal epicardial-derived cells (EPDCs), that contribute to the development of CVs and cardiac interstitium. 1 Proepicardial cells (proEPCs) can differentiate in vivo and in vitro into vascular/fibroblastic cell types or myocardium depending on the conditions. 3 A recent study proposed that proepicardial fate depends on the balance between Bmps and Fgfs signals, Bmps promoting myocardial differentiation and Fgfs f...

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Section: Del Monte Et Al Notch Expression and Function In The Epicardiummentioning

confidence: 97%

Differential Notch Signaling in the Epicardium Is Required for Cardiac Inflow Development and Coronary Vessel Morphogenesis

Monte

Casanova

Guadix

et al. 2011

Circulation Research

152

134

View full text Add to dashboard Cite

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“…5,61 This non-cell autonomous role of the epicardium is mediated by a characteristic epicardial secretome, including growth factors and other soluble molecules. Retinoic acid (RA) (mostly via Rxra) plays a key role in the production of part of this secretome, although RA itself does not promote growth of compact myocardium.…”

Section: Non-cell Autonomous Roles Of Epicardium In Heart Developmentmentioning

confidence: 99%

Signaling During Epicardium and Coronary Vessel Development

Pérez‐Pomares

Pompa

2011

Circulation Research

133

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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.)

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“…Coronary vascular development. Several reviews summarize what is known about coronary vascular development (Lie-Venema et al, 2007;Olivey et al, 2004;Olivey and Svensson, 2010;Reese et al, 2002;Tomanek, 2005;Wada, 2003;Wessels and PerezPomares, 2004). Precursors of the coronary vasculature are contributed by the embryonic epicardium that arises from the pro-epicardial serosa at a stage when chamber differentiation has begun (Hiruma and Hirakow, 1989;Ho and Shimada, 1978;Viragh and Challice, 1981).…”

Section: Where Do Endothelial Cells In the Heart Come From?mentioning

confidence: 99%