Coronary Vessel DevelopmentThe Epicardium Delivers

Olivey, Harold E.; Compton, Leigh A.; Barnett, Joey V.

doi:10.1016/s1050-1738(04)00110-0

Cited by 39 publications

(42 citation statements)

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“…Other investigators successfully have adapted this collagen culture system to examine EMT in PE explants (Mikawa and Gourdie, 1996;Dettman et al, 1998). Although the collagen matrix does not mimic the complex extracellular matrix environments found in either the endocardial cushions or the subepicardial matrix, this system does facilitate the study of the cellular behaviors that occur during EMT and has been used effectively to identify important signals that regulate EMT (Barnett and Desgrosellier, 2003;Olivey et al, 2004).…”

Section: Resultsmentioning

confidence: 99%

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Transforming growth factor‐β stimulates epithelial–mesenchymal transformation in the proepicardium

Olivey

Mundell

Austin

et al. 2005

Developmental Dynamics

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The proepicardium (PE) migrates over the heart and forms the epicardium. A subset of these PE-derived cells undergoes epithelial-mesenchymal transformation (EMT) and gives rise to cardiac fibroblasts and components of the coronary vasculature. We report that transforming growth factor-␤ (TGF␤) 1 and TGF␤2 increase EMT in PE explants as measured by invasion into a collagen gel, loss of cytokeratin expression, and redistribution of ZO1. The type I TGF␤ receptors ALK2 and ALK5 are both expressed in the PE. However, only constitutively active (ca) ALK2 stimulates PE-derived epithelial cell activation, the first step in transformation, whereas caALK5 stimulates neither activation nor transformation in PE explants. Overexpression of Smad6, an inhibitor of ALK2 signaling, inhibits epithelial cell activation, whereas BMP7, a known ligand for ALK2, has no effect. These data demonstrate that TGF␤ stimulates transformation in the PE and suggest that ALK2 partially mediates this effect. Developmental Dynamics 235:50 -59, 2006.

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Section: Resultsmentioning

confidence: 99%

“…Although it was long believed that coronary vessels formed by angiogenesis as an outgrowth of the proximal aorta, it is now recognized that the coronary vessels initially arise by vasculogenesis (Mikawa and Fischman, 1992;Olivey et al, 2004). Thus, vessels are well-formed before contacting and eventually penetrating the proximal aorta.…”

Section: Introductionmentioning

confidence: 99%

Transforming growth factor‐β stimulates epithelial–mesenchymal transformation in the proepicardium

Olivey

Mundell

Austin

et al. 2005

Developmental Dynamics

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“…Deficient coronary development precludes compaction and is the basis of embryonic lethality in mice lacking coronary arteries (Kwee et al, 1995); reviewed in , or, when localized, could be a cause of recently recognized noncompacted cardiomyopathy (Varnava, 2001). Molecular mechanisms orchestrating coupled development between myocardium and coronary vasculature were recently summarized by Bhattacharya et al (2006), whereas current views on the genetic pathways controlling development of the coronary vasculature were reviewed by Olivey et al (2004). However, recent experimental study by Lavine et al (2008) have pointed out that regulation of cell proliferation in myocardium and coronary vasculature utilizes genetically distinct pathways.…”

Section: Introductionmentioning

confidence: 99%

Abnormal Myocardial and Coronary Vasculature Development in Experimental Hypoxia

Naňka

Krizova

Fikrle

et al. 2008

The Anatomical Record

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Oxygen availability is one of the necessary prerequisites for normal embryonic development. In our previous study we found that quail embryos incubated under hypoxic conditions (16% O 2 ) die at embryonic day (ED) 9 with signs of heart failure. By ED4 and ED6 we found thinner ventricular wall and increased capillary density. We thus hypothesized that the cause of death would lie in severe myocardial and coronary maldevelopment. ED6 and 7 hypoxic hearts had thinner ventricular wall, especially left. There was a simultaneous increase in capillary density, most pronounced in the interventricular septum. This site corresponds to an area of tissue hypoxia and ensuing increased angiogenesis, and also formation of ventricular conduction system. Hypoxia had a positive effect on normal sequence of maturation of the conduction system evaluated by optical mapping at ED7. In sections from ED9 hypoxic hearts we found, in addition to thinner ventricular walls, irregularities in development of coronary tree (missing coronary ostia, absence of one coronary artery, and irregular arterial wall). This deficiency was due to decreased myocyte proliferation rather than to increased apoptosis. By Indian ink injection through the left ventricle we found in normoxic hearts regular coronary branching pattern, while in the hypoxic ones there was often only an irregular plexus. Embryonic hypoxia thus leads to increased capillarity and trabeculation to minimize diffusion distance. In the subsequent period there is a failure in organization of vascular plexus into normal vasculature, resulting in thin compact myocardium that likely leads to heart failure and embryonic death.

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“…EMT is a key step during heart development in mice and chicks, wherein the epicardium forms epicardium-derived cells (EPDCs), which then differentiate into fibroblasts, smooth muscle cells (7)(8)(9), and potential cardiomyocytes (10,11). The molecular aspects of zebrafish heart regeneration are poorly understood.…”

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confidence: 99%

PDGF signaling is required for epicardial function and blood vessel formation in regenerating zebrafish hearts

Kim¹,

Wu²,

Zhang³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

179

187

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A zebrafish heart can fully regenerate after amputation of up to 20% of its ventricle. During this process, newly formed coronary blood vessels revascularize the regenerating tissue. The formation of coronary blood vessels during zebrafish heart regeneration likely recapitulates embryonic coronary vessel development, which involves the activation and proliferation of the epicardium, followed by an epithelial-to-mesenchymal transition. The molecular and cellular mechanisms underlying these processes are not well understood. We examined the role of PDGF signaling in explantderived primary cultured epicardial cells in vitro and in regenerating zebrafish hearts in vivo. We observed that mural and mesenchymal cell markers, including pdgfrβ, are up-regulated in the regenerating hearts. Using a primary culture of epicardial cells derived from heart explants, we found that PDGF signaling is essential for epicardial cell proliferation. PDGF also induces stress fibers and loss of cell-cell contacts of epicardial cells in explant culture. This effect is mediated by Rhoassociated protein kinase. Inhibition of PDGF signaling in vivo impairs epicardial cell proliferation, expression of mesenchymal and mural cell markers, and coronary blood vessel formation. Our data suggest that PDGF signaling plays important roles in epicardial function and coronary vessel formation during heart regeneration in zebrafish.epicardium | mesenchymal cells | mural cells | zebrafish heart regeneration C oronary heart disease is among the leading causes of disability and mortality in the United States and worldwide (1). Scars form in injured human hearts, which results in decreased cardiac performance and the eventual development of heart failure (2). In contrast to humans, zebrafish and newts have remarkable regenerative abilities (3, 4). After 20% resection of the ventricle, zebrafish fully regenerate lost heart tissue (3, 4). During this process, newly formed coronary blood vessels vascularize the regenerating myocardium (5, 6). Expression of the embryonic epicardial markers tbx18 and raldh2 is induced in the epicardium of adult regenerating hearts (5, 6), suggesting that an embryonic gene expression program in the epicardium is activated in response to injury. This activation starts throughout the entire ventricle and gradually becomes localized to the apex. The activated epicardium proliferates from 3 to 7 d postamputation (dpa) (5). A previous study suggested that the activated epicardium undergoes an epithelial-to-mesenchymal transition (EMT) and subsequently contributes to newly formed coronary blood vessels (5). The lineages of the different cell types in blood vessels formed during zebrafish heart regeneration have not yet been conclusively determined.Zebrafish heart regeneration, at least in part, likely recapitulates embryonic heart development. EMT is a key step during heart development in mice and chicks, wherein the epicardium forms epicardium-derived cells (EPDCs), which then differentiate into fibroblasts, smooth muscle cells (7-9)...

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Coronary Vessel DevelopmentThe Epicardium Delivers

Cited by 39 publications

References 0 publications

Transforming growth factor‐β stimulates epithelial–mesenchymal transformation in the proepicardium

Transforming growth factor‐β stimulates epithelial–mesenchymal transformation in the proepicardium

Abnormal Myocardial and Coronary Vasculature Development in Experimental Hypoxia

PDGF signaling is required for epicardial function and blood vessel formation in regenerating zebrafish hearts

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