Molecular mechanisms that control endothelial cell contacts

Endothelial cells play a wide variety of critical roles in the control of vascular function. Indeed, since the early 1980s, the accumulating knowledge of the endothelial cell structure as well as of the functional properties of the endothelial cells shifted their role from a passive membrane or barrier to a complex tissue with complex functions adaptable to needs specific in time and location. Hence, it participates to all aspects of the vascular homeostasis but also to physiological or pathological processes like thrombosis, inflammation, or vascular wall remodeling. Some of the most important endothelial functions will be described in the following review and more specifically, their role in blood vessel formation, in coagulation and fibribolysis, in the regulation of vascular tone as well as their participation in inflammatory reactions and in tumor neoangiogenesis. J. Cell. Physiol. 196: 430–443, 2003. © 2003 Wiley‐Liss, Inc.

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“…. but the detailed structure of this complex is not yet determined (Bazzoni et al, 1999;Vestweber, 2000).…”

Section: Endothelial Cell Barriermentioning

confidence: 99%

Endothelial cell functions

Michiels

2003

Journal Cellular Physiology

614

429

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“…We were especially surprised by the identification of desmocollin I in the aorta, because desmosomes have not been detected in ultrastructural analysis of large vessels. 29 Expression of other desmosomal cadherins, desmocollin 2 and desmoglein 2, was also detected in low levels in both aorta and IVC, with similar signal intensity (data not shown), whereas desmocollin 3 was undetectable in both murine aorta and IVC. Plakophilin I is a member of the armadillo family of arm proteins that directly interact with cadherins located in both adherens junctions and desmosomes (Table 1).…”

Section: Cell Adhesive Junction-related Genes Are Enriched In the Aormentioning

confidence: 99%

“…Plakophilin I is a member of the armadillo family of arm proteins that directly interact with cadherins located in both adherens junctions and desmosomes (Table 1). 29 These junctions play an important role in providing strength to tissues that experience mechanical stress, such as heart and epidermis, and are highly expressed in these tissues. 29 -31 Plakoglobin belongs to the same family as plakophilin I, has a similar role in adhesive junctions, and has been shown to be important in interendothelial adhesion during shear stress.…”

Section: Cell Adhesive Junction-related Genes Are Enriched In the Aormentioning

confidence: 99%

Enrichment of Genes in the Aortic Intima That Are Associated With Stratified Epithelium

et al. 2005

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Background-Arteries and veins are exposed to different pressures and are easily distinguished by morphology. Although several recent studies have focused on differential gene expression between the arterial and venous endothelium, the molecular distinctions that give rise to the dramatic structural distinctions between arteries and veins, such as in the organization of the intima, are not known. Methods and Results-We used high-density oligonucleotide arrays to analyze the transcriptional profile of the mouse aorta and inferior vena cava (IVC), not restricting our analysis to the endothelium, to identify genes whose expression was enriched in aorta over other tissues and the IVC. By quantitative reverse transcription-polymerase chain reaction analysis, these genes have been shown to be highly expressed in the mouse aorta and were either expressed at low levels or were undetectable in the murine IVC. By immunofluorescence analysis of human tissue, we determined that a subset of these aorta-enriched proteins exhibited a primarily intima-restricted expression. Intimal expression of at least a subset of these genes, plakoglobin, galectin 7, sciellin, and SPRR3, was also detected in other types of arteries but not in veins. Furthermore, SPRR3 expression in the intima was primarily associated with atheromas. The proteins identified are functionally related in that they are known to also be enriched in stratified epithelia, where they play an important role in stress-bearing and barrier properties. Conclusions-Vascular expression of these genes has not been reported previously. Our observations suggest that they may play a significant role in the mechanisms by which large arteries may adapt to biomechanical stress.

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“…In the endothelium, where a single layer of cells separates tissues from their blood supply, the concerted regulation of cell-cell and cell-ECM adhesion drives rapid changes in cell shape and vascular architecture essential to vascular remodeling in both normal and disease processes (Vestweber, 2000;Dudek and Garcia, 2001). Dynamic changes in cell-cell and cell-matrix adhesion and mechanical forces are responsible for regulating vascular permeability, and agents that alter permeability invariably affect both types of adhesion complexes (Dudek and Garcia, 2001).…”

Section: Introductionmentioning

confidence: 99%

Vascular Endothelial-Cadherin Regulates Cytoskeletal Tension, Cell Spreading, and Focal Adhesions by Stimulating RhoA

Nelson

Pirone

Tan

et al. 2004

MBoC

165

137

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Changes in vascular endothelial (VE)-cadherin-mediated cell-cell adhesion and integrin-mediated cell-matrix adhesion coordinate to affect the physical and mechanical rearrangements of the endothelium, although the mechanisms for such cross talk remain undefined. Herein, we describe the regulation of focal adhesion formation and cytoskeletal tension by intercellular VE-cadherin engagement, and the molecular mechanism by which this occurs. Increasing the density of endothelial cells to increase cell-cell contact decreased focal adhesions by decreasing cell spreading. This contact inhibition of cell spreading was blocked by disrupting VE-cadherin engagement with an adenovirus encoding dominant negative VE-cadherin. When changes in cell spreading were prevented by culturing cells on a micropatterned substrate, VE-cadherin-mediated cell-cell contact paradoxically increased focal adhesion formation. We show that VE-cadherin engagement mediates each of these effects by inducing both a transient and sustained activation of RhoA. Both the increase and decrease in cell-matrix adhesion were blocked by disrupting intracellular tension and signaling through the Rho-ROCK pathway. In all, these findings demonstrate that VE-cadherin signals through RhoA and the actin cytoskeleton to cross talk with cell-matrix adhesion and thereby define a novel pathway by which cell-cell contact alters the global mechanical and functional state of cells. INTRODUCTIONCoordinated changes between cell adhesion to the extracellular matrix (ECM) and to neighboring cells are crucial for the many physical transformations that cells must undergo during development, tissue homeostasis, and wound healing. In the endothelium, where a single layer of cells separates tissues from their blood supply, the concerted regulation of cell-cell and cell-ECM adhesion drives rapid changes in cell shape and vascular architecture essential to vascular remodeling in both normal and disease processes (Vestweber, 2000;Dudek and Garcia, 2001). Dynamic changes in cell-cell and cell-matrix adhesion and mechanical forces are responsible for regulating vascular permeability, and agents that alter permeability invariably affect both types of adhesion complexes (Dudek and Garcia, 2001). During blood vessel sprouting and migration in angiogenesis, endothelial cells must disassemble and reform their cell-cell and cell-ECM contacts in synchrony to generate appropriate structures. These two adhesion systems each regulate their functional effects through both biochemical and mechanical signals.Changes in integrin binding to ECM not only alter signals that regulate cell proliferation, migration, and survival (Assoian and Schwartz, 2001;Hood and Cheresh, 2002;Stupack and Cheresh, 2002) but also modulate cell mechanics by affecting focal adhesion (FA) maturation, adhesion strength, cytoskeletal contractility, and cell shape (Geiger and Bershadsky, 2002;Juliano, 2002). Likewise, changes in the engagement of vascular endothelial (VE)-cadherin, the principal junctional molecule in endothe...

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Molecular mechanisms that control endothelial cell contacts

Cited by 114 publications

References 145 publications

Endothelial cell functions

Endothelial cell functions

Enrichment of Genes in the Aortic Intima That Are Associated With Stratified Epithelium

Vascular Endothelial-Cadherin Regulates Cytoskeletal Tension, Cell Spreading, and Focal Adhesions by Stimulating RhoA

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