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Arterioscler Thromb Vasc Biol. 2014 Sep;34(9):2059-67. doi: 10.1161/ATVBAHA.114.304180. Epub 2014 Jul 10.

F-actin-anchored focal adhesions distinguish endothelial phenotypes of human arteries and veins.

Author information

1
From the Department of Molecular Cell Biology, Sanquin Research and Swammerdam Institute for Life Sciences, Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (D.v.G., M.W.J.S., A.-M.D.v.S., P.L.H., S.H.); Department of Plastic and Reconstructive Surgery, the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands (L.A.E.W.); and Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (M.J.A.P.D.).
2
From the Department of Molecular Cell Biology, Sanquin Research and Swammerdam Institute for Life Sciences, Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (D.v.G., M.W.J.S., A.-M.D.v.S., P.L.H., S.H.); Department of Plastic and Reconstructive Surgery, the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands (L.A.E.W.); and Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (M.J.A.P.D.). s.huveneers@sanquin.nl.

Abstract

OBJECTIVE:

Vascular endothelial-cadherin- and integrin-based cell adhesions are crucial for endothelial barrier function. Formation and disassembly of these adhesions controls endothelial remodeling during vascular repair, angiogenesis, and inflammation. In vitro studies indicate that vascular cytokines control adhesion through regulation of the actin cytoskeleton, but it remains unknown whether such regulation occurs in human vessels. We aimed to investigate regulation of the actin cytoskeleton and cell adhesions within the endothelium of human arteries and veins.

APPROACH AND RESULTS:

We used an ex vivo protocol for immunofluorescence in human vessels, allowing detailed en face microscopy of endothelial monolayers. We compared arteries and veins of the umbilical cord and mesenteric, epigastric, and breast tissues and find that the presence of central F-actin fibers distinguishes the endothelial phenotype of adult arteries from veins. F-actin in endothelium of adult veins as well as in umbilical vasculature predominantly localizes cortically at the cell boundaries. By contrast, prominent endothelial F-actin fibers in adult arteries anchor mostly to focal adhesions containing integrin-binding proteins paxillin and focal adhesion kinase and follow the orientation of the extracellular matrix protein fibronectin. Other arterial F-actin fibers end in vascular endothelial-cadherin-based endothelial focal adherens junctions. In vitro adhesion experiments on compliant substrates demonstrate that formation of focal adhesions is strongly induced by extracellular matrix rigidity, irrespective of arterial or venous origin of endothelial cells.

CONCLUSIONS:

Our data show that F-actin-anchored focal adhesions distinguish endothelial phenotypes of human arteries from veins. We conclude that the biomechanical properties of the vascular extracellular matrix determine this endothelial characteristic.

KEYWORDS:

arteries; focal adhesions

PMID:
25012130
DOI:
10.1161/ATVBAHA.114.304180
[Indexed for MEDLINE]

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