scholarly journals Coronary arterial development is regulated by a Dll4-Jag1-EphrinB2 signaling cascade

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Stanislao Igor Travisano ◽  
Vera Lucia Oliveira ◽  
Belén Prados ◽  
Joaquim Grego-Bessa ◽  
Rebeca Piñeiro-Sabarís ◽  
...  

Coronaries are essential for myocardial growth and heart function. Notch is crucial for mouse embryonic angiogenesis, but its role in coronary development remains uncertain. We show Jag1, Dll4 and activated Notch1 receptor expression in sinus venosus (SV) endocardium. Endocardial Jag1 removal blocks SV capillary sprouting, while Dll4 inactivation stimulates excessive capillary growth, suggesting that ligand antagonism regulates coronary primary plexus formation. Later endothelial ligand removal, or forced expression of Dll4 or the glycosyltransferase Mfng, blocks coronary plexus remodeling, arterial differentiation, and perivascular cell maturation. Endocardial deletion of Efnb2 phenocopies the coronary arterial defects of Notch mutants. Angiogenic rescue experiments in ventricular explants, or in primary human endothelial cells, indicate that EphrinB2 is a critical effector of antagonistic Dll4 and Jag1 functions in arterial morphogenesis. Thus, coronary arterial precursors are specified in the SV prior to primary coronary plexus formation and subsequent arterial differentiation depends on a Dll4-Jag1-EphrinB2 signaling cascade.

2019 ◽  
Author(s):  
Stanislao Igor Travisano ◽  
Vera Lucia Oliveira ◽  
Belén Prados ◽  
Joaquim Grego-Bessa ◽  
Vanesa Bou ◽  
...  

AbstractCoronaries are essential for myocardial growth and heart function. Notch is crucial for mouse embryonic angiogenesis, but its role in coronary development remains uncertain. We show Jag1, Dll4 and activated Notch1 receptor expression in sinus venosus (SV) endocardium. Endocardial Jag1 removal blocks SV capillary sprouting, while Dll4 inactivation stimulates excessive capillary growth, suggesting that ligand antagonism regulates coronary primary plexus formation. Later endothelial ligand removal, or forced expression of Dll4 or the glycosyltransferase MFng, blocks coronary plexus remodeling, arterial differentiation, and perivascular cell maturation. Endocardial deletion of Efnb2 phenocopies the coronary arterial defects of Notch mutants. Angiogenic rescue experiments in ventricular explants, or in primary human endothelial cells, indicate that EphrinB2 is a critical effector of antagonistic Dll4 and Jag1 functions in arterial morphogenesis. Thus, coronary arterial precursors are specified in the SV prior to primary coronary plexus formation and subsequent arterial differentiation depends on a Dll4-Jag1-EphrinB2 signaling cascade.


1997 ◽  
Vol 56 ◽  
pp. 101 ◽  
Author(s):  
C. Murdoch ◽  
P.N. Monk ◽  
J.E. Pease ◽  
M.D. Barker ◽  
A. Finn

Virology ◽  
1990 ◽  
Vol 174 (1) ◽  
pp. 95-102 ◽  
Author(s):  
Thérèse Couderc ◽  
Thérèse Barzu ◽  
Florian Horaud ◽  
Radu Crainic

2001 ◽  
Vol 85 (02) ◽  
pp. 296-302 ◽  
Author(s):  
Marielle Kroon ◽  
Pieter Koolwijk ◽  
Mario Vermeer ◽  
Bea van der Vecht ◽  
Victor van Hinsbergh

SummaryAmong other proteolytic enzymes, the urokinase-type plasminogen activator (u-PA)/plasmin cascade contributes to cell migration and the formation of capillary-like structures in a fibrinous exudate. The u-PA receptor (u-PAR) focuses proteolytical activity on the cell surface of the endothelial cell and hereby accelerates the pericellular matrix degradation. Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF)-2 enhance u-PA receptor expression in human endothelial cells. In this paper we show that the protein kinase C (PKC) inhibitors Ro31-8220 and GF109203X inhibit VEGF165-induced u-PAR antigen expression in human endothelial cells, whereas PKC inhibition had no effect on FGF-2-induced u-PAR antigen enhancement. In addition, inhibition of PKC activity had no effect on VEGF165-or FGF-2-induced proliferation in human endothelial cells. We conclude that VEGF165 induces u-PAR via a PKC-dependent pathway, whereas proliferation is induced via a different pathway probably involving tyrosine phosphorylation of proteins downstream of the VEGF receptors.


2006 ◽  
Vol 188 (1) ◽  
pp. 51-58 ◽  
Author(s):  
Niels R. Veillard ◽  
Vincent Braunersreuther ◽  
Claire Arnaud ◽  
Fabienne Burger ◽  
Graziano Pelli ◽  
...  

2000 ◽  
Vol 87 (5) ◽  
pp. 370-377 ◽  
Author(s):  
Carsten Willam ◽  
Petra Koehne ◽  
Jan Steffen Jürgensen ◽  
Michael Gräfe ◽  
Kay Dietrich Wagner ◽  
...  

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