Faculty Opinions recommendation of Angiopoietins assemble distinct Tie2 signalling complexes in endothelial cell-cell and cell-matrix contacts.

Polyurethanes (PUs) are composed of soft and hard segments, and segmental interactions induce biphasic morphologies which can influence endothelial cell (EC) organization by regulating cell–matrix and cell–cell interactions. In this study, we explored this effect using poly(caprolactone) (PCL)-based PU, where the soft segment was composed of PCL and the hard segment was composed of hexamethylene diisocyanate (HDI) and L-tyrosine-based dipeptide (DTH). The composition of the PUs was varied by altering the PCL molecular weight and correspondingly, different phase morphologies were observed. Organization and functional state of ECs on these PUs showed that composition and phase morphology of PU have a significant effect on cellular response. The ECs formed an organized network with cord-like structures which resulted in interconnected loops when soft and hard segment fractions were phase-separated. VE-cadherin (for cell–cell adherence) and vinculin (for cell–matrix focal adhesion) localized at the tip of interconnecting cells in the tube structures indicated synchronized cell–cell and cell–matrix interactions.

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Tetraspanin CD151 maintains vascular stability by balancing the forces of cell adhesion and cytoskeletal tension

Blood ◽

10.1182/blood-2011-03-339531 ◽

2011 ◽

Vol 118 (15) ◽

pp. 4274-4284 ◽

Cited By ~ 30

Author(s):

Feng Zhang ◽

Jarett E. Michaelson ◽

Simon Moshiach ◽

Norman Sachs ◽

Wenyuan Zhao ◽

...

Keyword(s):

Cell Adhesion ◽

Endothelial Cell ◽

Cell Matrix ◽

Vascular Morphogenesis ◽

Vascular Stability ◽

Optimal Functions ◽

Cytoskeletal Tension ◽

Cell Cell

Abstract Tetraspanin CD151 is highly expressed in endothelial cells and regulates pathologic angiogenesis. However, the mechanism by which CD151 promotes vascular morphogenesis and whether CD151 engages other vascular functions are unclear. Here we report that CD151 is required for maintaining endothelial capillary-like structures formed in vitro and the integrity of endothelial cell-cell and cell-matrix contacts in vivo. In addition, vascular permeability is markedly enhanced in the absence of CD151. As a global regulator of endothelial cell-cell and cell-matrix adhesions, CD151 is needed for the optimal functions of various cell adhesion proteins. The loss of CD151 elevates actin cytoskeletal traction by up-regulating RhoA signaling and diminishes actin cortical meshwork by down-regulating Rac1 activity. The inhibition of RhoA or activation of cAMP signaling stabilizes CD151-silenced or -null endothelial structure in vascular morphogenesis. Together, our data demonstrate that CD151 maintains vascular stability by promoting endothelial cell adhesions, especially cell-cell adhesion, and confining cytoskeletal tension.

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Angiopoietins assemble distinct Tie2 signalling complexes in endothelial cell–cell and cell–matrix contacts

Nature Cell Biology ◽

10.1038/ncb1715 ◽

2008 ◽

Vol 10 (5) ◽

pp. 527-537 ◽

Cited By ~ 283

Author(s):

Pipsa Saharinen ◽

Lauri Eklund ◽

Juho Miettinen ◽

Riikka Wirkkala ◽

Andrey Anisimov ◽

...

Keyword(s):

Endothelial Cell ◽

Cell Matrix ◽

Cell Cell

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Faculty Opinions recommendation of Angiopoietins assemble distinct Tie2 signalling complexes in endothelial cell-cell and cell-matrix contacts.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1115426.572693 ◽

2008 ◽

Author(s):

Andrius Kazlauskas

Keyword(s):

Endothelial Cell ◽

Cell Matrix ◽

Cell Cell

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PECAM-1 regulates proangiogenic properties of endothelial cells through modulation of cell-cell and cell-matrix interactions

AJP Cell Physiology ◽

10.1152/ajpcell.00246.2010 ◽

2010 ◽

Vol 299 (6) ◽

pp. C1468-C1484 ◽

Cited By ~ 45

Author(s):

SunYoung Park ◽

Terri A. DiMaio ◽

Elizabeth A. Scheef ◽

Christine M. Sorenson ◽

Nader Sheibani

Keyword(s):

Nitric Oxide ◽

Endothelial Cells ◽

Cell Adhesion ◽

Endothelial Cell ◽

Immunoglobulin Superfamily ◽

Capillary Morphogenesis ◽

Cell Matrix ◽

Matrix Interactions ◽

Cell Matrix Interactions ◽

Cell Cell

Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) is a member of the immunoglobulin superfamily of cell adhesion molecules with important roles in angiogenesis and inflammation. However, the molecular and cellular mechanisms, and the role that specific PECAM-1 isoforms play in these processes, remain elusive. We recently showed attenuation of retinal vascular development and neovascularization in PECAM-1-deficient (PECAM-1−/−) mice. To gain further insight into the role of PECAM-1 in these processes, we isolated primary retinal endothelial cells (EC) from wild-type (PECAM-1+/+) and PECAM-1−/− mice. Lack of PECAM-1 had a significant impact on endothelial cell-cell and cell-matrix interactions, resulting in attenuation of cell migration and capillary morphogenesis. Mechanistically these changes were associated with a significant decrease in expression of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) bioavailability in PECAM-1−/− retinal EC. PECAM-1−/− retinal EC also exhibited a lower rate of apoptosis under basal and challenged conditions, consistent with their increased growth rate. Furthermore, reexpression of PECAM-1 was sufficient to restore migration and capillary morphogenesis of null cells in an isoform-specific manner. Thus PECAM-1 expression modulates proangiogenic properties of EC, and these activities are significantly influenced by alternative splicing of its cytoplasmic domain.

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Cleavage of β-Catenin and Plakoglobin and Shedding of VE-Cadherin during Endothelial Apoptosis: Evidence for a Role for Caspases and Metalloproteinases

Molecular Biology of the Cell ◽

10.1091/mbc.9.6.1589 ◽

1998 ◽

Vol 9 (6) ◽

pp. 1589-1601 ◽

Cited By ~ 195

Author(s):

Barbara Herren ◽

Bodo Levkau ◽

Elaine W. Raines ◽

Russell Ross

Keyword(s):

Endothelial Cell ◽

Binding Capacity ◽

Adherens Junctions ◽

Proteolytic Processing ◽

Actin Binding ◽

Apoptotic Cells ◽

Endothelial Apoptosis ◽

Cell Matrix ◽

Cell Cell

Growth factor deprivation of endothelial cells induces apoptosis, which is characterized by membrane blebbing, cell rounding, and subsequent loss of cell–matrix and cell–cell contacts. In this study, we show that initiation of endothelial apoptosis correlates with cleavage and disassembly of intracellular and extracellular components of adherens junctions. β-Catenin and plakoglobin, which form intracellular links between vascular endothelial cadherin (VE-cadherin) and actin-binding α-catenin in adherens junctions, are cleaved in apoptotic cells. In vitro incubations of cell lysates and immunoprecipitates with recombinant caspases indicate that CPP32 and Mch2 are involved, possibly by initiating proteolytic processing. Cleaved β-catenin from lysates of apoptotic cells does not bind to endogenous α-catenin, whereas plakoglobin retains its binding capacity. The extracellular portion of the adherens junctions is also altered during apoptosis because VE-cadherin, which mediates endothelial cell–cell interactions, dramatically decreases on the surface of cells. An extracellular fragment of VE-cadherin can be detected in the conditioned medium, and this “shedding” of VE-cadherin can be blocked by an inhibitor of metalloproteinases. Thus, cleavage of β-catenin and plakoglobin and shedding of VE-cadherin may act in concert to disrupt structural and signaling properties of adherens junctions and may actively interrupt extracellular signals required for endothelial cell survival.

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