scholarly journals Dynamic Endothelial Cell Rearrangements Drive Developmental Vessel Regression

PLoS Biology ◽  
2015 ◽  
Vol 13 (4) ◽  
pp. e1002125 ◽  
Author(s):  
Claudio A. Franco ◽  
Martin L. Jones ◽  
Miguel O. Bernabeu ◽  
Ilse Geudens ◽  
Thomas Mathivet ◽  
...  
PLoS Biology ◽  
2015 ◽  
Vol 13 (5) ◽  
pp. e1002163 ◽  
Author(s):  
Claudio A. Franco ◽  
Martin L. Jones ◽  
Miguel O. Bernabeu ◽  
Ilse Geudens ◽  
Thomas Mathivet ◽  
...  

Development ◽  
2016 ◽  
Vol 143 (16) ◽  
pp. 2973-2982 ◽  
Author(s):  
Emma C. Watson ◽  
Monica N. Koenig ◽  
Zoe L. Grant ◽  
Lachlan Whitehead ◽  
Evelyn Trounson ◽  
...  

2017 ◽  
Vol 74 (24) ◽  
pp. 4387-4403 ◽  
Author(s):  
Emma C. Watson ◽  
Zoe L. Grant ◽  
Leigh Coultas

Blood ◽  
2012 ◽  
Vol 120 (7) ◽  
pp. 1516-1527 ◽  
Author(s):  
Nicole Simonavicius ◽  
Matthew Ashenden ◽  
Antoinette van Weverwijk ◽  
Siân Lax ◽  
David L. Huso ◽  
...  

Abstract Blood vessel networks form in a 2-step process of sprouting angiogenesis followed by selective branch regression and stabilization of remaining vessels. Pericytes are known to function in stabilizing blood vessels, but their role in vascular sprouting and selective vessel regression is poorly understood. The endosialin (CD248) receptor is expressed by pericytes associated with newly forming but not stable quiescent vessels. In the present study, we used the Endosialin−/− mouse as a means to uncover novel roles for pericytes during the process of vascular network formation. We demonstrate in a postnatal retina model that Endosialin−/− mice have normal vascular sprouting but are defective in selective vessel regression, leading to increased vessel density. Examination of the Endosialin−/− mouse tumor vasculature revealed an equivalent phenotype, indicating that pericytes perform a hitherto unidentified function to promote vessel destabilization and regression in vivo in both physiologic and pathologic angiogenesis. Mechanistically, Endosialin−/− mice have no defect in pericyte recruitment. Rather, endosialin binding to an endothelial associated, but not a pericyte associated, basement membrane component induces endothelial cell apoptosis and detachment. The results of the present study advance our understanding of pericyte biology and pericyte/endothelial cell cooperation during vascular patterning and have implications for the design of both pro- and antiangiogenic therapies.


2000 ◽  
Vol 87 (6) ◽  
pp. 434-439 ◽  
Author(s):  
Stefanie Dimmeler ◽  
Andreas M. Zeiher

Author(s):  
T. M. Murad ◽  
E. von Haam

Pericytes are vascular satellites present around capillary blood vessels and small venules. They have been observed in almost every tissue of the body and are thought to be related to vascular smooth muscle cells. Morphologically pericytes have great similarity to vascular endothelial cells and also slightly resemble myoepithelial cells.The present study describes the ultrastructural morphology of pericytes in normal breast tissue and in benign tumor of the breast. The study showed that pericytes are ovoid or elongated cells separated from the endothelial cell of the capillary blood vessel by the basement membrane of endothelial cell. The nuclei of pericytes are often very distinctive. Although some are round, oval, or elongated, others show marked irregularity and infolding of the nuclear membrane. The cytoplasm shows mono-or bipolar extension in which the cytoplasmic organelles are located (Fig. 1). These cytoplasmic extensions embrace the capillary blood vessel incompletely. The plasma membrane exhibits multiple areas of focal condensation called hemidesmosomes (Fig. 2, arrow). A variable number of pinocytotic vesicles are frequently seen lining the outer plasma membrane. Normally pericytes are surrounded by a basement membrane which is found more consistently on the outer plasma membrane separating the pericytes from the stromal connective tissue.


2010 ◽  
Vol 34 (8) ◽  
pp. S71-S71
Author(s):  
Xiaohui Shen ◽  
Zhi‑Bin Wen ◽  
Na Li ◽  
Qingmei Cheng ◽  
Xiaofan He ◽  
...  

2019 ◽  
Vol 133 (20) ◽  
pp. 2045-2059 ◽  
Author(s):  
Da Zhang ◽  
Xiuli Wang ◽  
Siyao Chen ◽  
Selena Chen ◽  
Wen Yu ◽  
...  

Abstract Background: Pulmonary artery endothelial cell (PAEC) inflammation is a critical event in the development of pulmonary arterial hypertension (PAH). However, the pathogenesis of PAEC inflammation remains unclear. Methods: Purified recombinant human inhibitor of κB kinase subunit β (IKKβ) protein, human PAECs and monocrotaline-induced pulmonary hypertensive rats were employed in the study. Site-directed mutagenesis, gene knockdown or overexpression were conducted to manipulate the expression or activity of a target protein. Results: We showed that hydrogen sulfide (H2S) inhibited IKKβ activation in the cell model of human PAEC inflammation induced by monocrotaline pyrrole-stimulation or knockdown of cystathionine γ-lyase (CSE), an H2S generating enzyme. Mechanistically, H2S was proved to inhibit IKKβ activity directly via sulfhydrating IKKβ at cysteinyl residue 179 (C179) in purified recombinant IKKβ protein in vitro, whereas thiol reductant dithiothreitol (DTT) reversed H2S-induced IKKβ inactivation. Furthermore, to demonstrate the significance of IKKβ sulfhydration by H2S in the development of PAEC inflammation, we mutated C179 to serine (C179S) in IKKβ. In purified IKKβ protein, C179S mutation of IKKβ abolished H2S-induced IKKβ sulfhydration and the subsequent IKKβ inactivation. In human PAECs, C179S mutation of IKKβ blocked H2S-inhibited IKKβ activation and PAEC inflammatory response. In pulmonary hypertensive rats, C179S mutation of IKKβ abolished the inhibitory effect of H2S on IKKβ activation and pulmonary vascular inflammation and remodeling. Conclusion: Collectively, our in vivo and in vitro findings demonstrated, for the first time, that endogenous H2S directly inactivated IKKβ via sulfhydrating IKKβ at Cys179 to inhibit nuclear factor-κB (NF-κB) pathway activation and thereby control PAEC inflammation in PAH.


Sign in / Sign up

Export Citation Format

Share Document