scholarly journals Vinculin Controls Endothelial Cell Junction Dynamics During Vascular Lumen Formation

2021 ◽  
Author(s):  
Maria P. Kotini ◽  
Miesje M. van der Stoel ◽  
Mitchell K. Han ◽  
Bettina Kirchmaier ◽  
Johan de Rooij ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Junction ◽  
Lumen Formation ◽  
Vascular Lumen

scholarly journals Vinculin controls endothelial cell junction dynamics during vascular lumen formation

2021 ◽  
Author(s):  
Maria P. Kotini ◽  
Miesje M. van der Stoel ◽  
Mitchell K. Han ◽  
Bettina Kirchmaier ◽  
Johan de Rooij ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Junctions ◽  
Cell Junction ◽  
Vascular Integrity ◽  
Lumen Formation ◽  
Cell Behaviors ◽  
Sprouting Angiogenesis ◽  
Dynamic Cell ◽  
External Forces ◽  
Cell Cell

AbstractBlood vessel morphogenesis is driven by coordinated endothelial cell behaviors, which depend on dynamic cell-cell interactions. Remodeling of endothelial cell-cell junctions promote morphogenetic cellular events while preserving vascular integrity. Here, we have analyzed the dynamics of endothelial cell-cell junctions during lumen formation in angiogenic sprouts. By live-imaging of the formation of intersegmental blood vessels in zebrafish, we demonstrate that lumen expansion is accompanied by the formation of transient finger-shaped junctions. Formation and maintenance of these junctional fingers are positively regulated by blood pressure whereas inhibition of blood flow prevents their formation. Using fluorescent reporters, we show that the tension-sensor Vinculin localizes to junctional fingers. Furthermore, loss of vinculin function, in vinculin a and -b double knockouts, prevents junctional finger formation in angiogenic sprouts, whereas endothelial expression of a vinculin transgene is sufficient to restore junctional fingers. Taken together, our findings suggest a mechanism in which lumen expansion during angiogenesis leads to an increase in junctional tension, which triggers recruitment of vinculin and formation of junctional fingers. We propose that endothelial cells may employ force-dependent junctional remodeling to react to changes in external forces to protect cell-cell contacts and to maintain vascular integrity during sprouting angiogenesis.

scholarly journals Molecular Mechanisms Controlling Vascular Lumen Formation in Three-Dimensional Extracellular Matrices

2012 ◽  
Vol 195 (1-2) ◽  
pp. 122-143 ◽  
Author(s):  
Anastasia Sacharidou ◽  
Amber N. Stratman ◽  
George E. Davis
Keyword(s):  
Molecular Mechanisms ◽  
Three Dimensional ◽  
Extracellular Matrices ◽  
Lumen Formation ◽  
Vascular Lumen

scholarly journals Vascular Lumen Formation: Negativity Will Tear Us Apart

2010 ◽  
Vol 20 (22) ◽  
pp. R973-R975 ◽  
Author(s):  
Renée M. Robbins ◽  
Greg J. Beitel
Keyword(s):  
Lumen Formation ◽  
Vascular Lumen

scholarly journals Rap1 Is Involved in Angiopoietin-1-Induced Cell-Cell Junction Stabilization and Endothelial Cell Sprouting

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 155
Author(s):  
Vanda Gaonac’h-Lovejoy ◽  
Cécile Boscher ◽  
Chantal Delisle ◽  
Jean-Philippe Gratton
Keyword(s):  
Endothelial Cell ◽  
Endothelial Permeability ◽  
Intercellular Junctions ◽  
Small Gtpase ◽  
Endothelial Barrier ◽  
Cell Junction ◽  
Barrier Integrity ◽  
Rap1 Activation ◽  
Angiopoietin 1 ◽  
Cell Cell

Angiopoietin-1 (Ang-1) is an important proangiogenic factor also involved in the maintenance of endothelial-barrier integrity. The small GTPase Rap1 is involved in the regulation of adherens junctions through VE-cadherin-mediated adhesion, and in endothelial permeability. While many studies established that Rap1 activation is critical for endothelial cell–cell adhesions, its roles in the antipermeability effects of Ang-1 are ill-defined. Thus, we determined the contribution of Rap1 to Ang-1-stimulated angiogenic effects on endothelial cells (ECs). We found that Rap1 is activated following Ang-1 stimulation and is required for the antipermeability effects of Ang-1 on EC monolayers. Our results also revealed that Rap1 is necessary for EC sprouting stimulated by Ang-1 but had no significant effect on Ang-1-induced EC migration and adhesion. In contrast, downregulation of VE-cadherin markedly increased the adhesiveness of ECs to the substratum, which resulted in inhibition of Ang-1-stimulated migration. These results revealed that Rap1 is central to the effects of Ang-1 at intercellular junctions of ECs, whereas VE-cadherin is also involved in the adhesion of ECs to the extracellular matrix.

scholarly journals Shear-induced endothelial cell-cell junction inclination

2010 ◽  
Vol 299 (3) ◽  
pp. C621-C629 ◽  
Author(s):  
Benoît Melchior ◽  
John A. Frangos
Keyword(s):  
Endothelial Cell ◽  
Flow Direction ◽  
Cell Junction ◽  
Structural Basis ◽  
Retrograde Flow ◽  
Arterial Circulation ◽  
Mouse Aorta ◽  
Cell Cell

Atheroprone regions of the arterial circulation are characterized by time-varying, reversing, and oscillatory wall shear stress. Several in vivo and in vitro studies have demonstrated that flow reversal (retrograde flow) is atherogenic and proinflammatory. The molecular and structural basis for the sensitivity of the endothelium to flow direction, however, has yet to be determined. It has been hypothesized that the ability to sense flow direction is dependent on the direction of inclination of the interendothelial junction. Immunostaining of the mouse aorta revealed an inclination of the cell-cell junction by 13° in direction of flow in the descending aorta where flow is unidirectional. In contrast, polygonal cells of the inner curvature where flow is disturbed did not have any preferential inclination. Using a membrane specific dye, the angle of inclination of the junction was dynamically monitored using live cell confocal microscopy in confluent human endothelial cell monolayers. Upon application of shear the junctions began inclining within minutes to a final angle of 10° in direction of flow. Retrograde flow led to a reversal of junctional inclination. Flow-induced junctional inclination was shown to be independent of the cytoskeleton or glycocalyx. Additionally, within seconds, retrograde flow led to significantly higher intracellular calcium responses than orthograde flow. Together, these results show for the first time that the endothelial intercellular junction inclination is dynamically responsive to flow direction and confers the ability to endothelial cells to rapidly sense and adapt to flow direction.

Attenuation of IL-2-induced multisystem organ edema by phalloidin and antamanide

1991 ◽  
Vol 70 (3) ◽  
pp. 1364-1368 ◽  
Author(s):  
R. Welbourn ◽  
G. Goldman ◽  
L. Kobzik ◽  
C. R. Valeri ◽  
H. B. Hechtman ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Side Effects ◽  
Bronchoalveolar Lavage ◽  
Protein Concentration ◽  
Interleukin 2 ◽  
Cell Junction ◽  
Elevated Protein ◽  
Intravenous Saline

Interleukin 2 (IL-2) is a potent cytokine with diverse effects, including the ability to stimulate lymphocyte differentiation into cells capable of lysing tumor. Its therapeutic efficacy is limited because of side effects such as breakdown of the microvascular barrier and edema. Control of the microvascular barrier is in part regulated by endothelial cell cytoskeletal contractile proteins. This study tests whether the cyclopeptides that maintain actin filament organization and distribution and reduce macromolecular flux across the endothelial cell junction in vitro would similarly maintain barrier tightness and prevent early edema produced by IL-2 in vivo. Anesthetized rats were treated at 30-min periods with intravenous saline (0.5 ml, n = 41), phalloidin (20 micrograms in 0.5 ml, n = 21), or antamanide, (20 micrograms in 0.5 ml, n = 21), starting 30 min before the 1-h infusion of 10(6) U of recombinant human IL-2 or saline. Six hours after the start of IL-2, there was edema in the saline/IL-2 group, as measured by increased wet-to-dry ratios (W/D) in the lungs, heart, and kidney. With saline/IL-2, bronchoalveolar lavage (BAL) fluid contained an elevated protein concentration and higher plasma thromboxane levels compared with controls. The number of neutrophils sequestered in the lungs was more than twice that of saline controls. Phalloidin significantly attenuated edema in lung and reduced BAL protein leak. Antamanide treatment was as effective in limiting lung and heart edema, but, in contrast to phalloidin, antamanide prevented kidney edema and did not lead to an alteration in the liver W/D. Antamanide also prevented BAL fluid protein leak.(ABSTRACT TRUNCATED AT 250 WORDS)

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