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

Daphne Van Geemen, Michel W.J. Smeets, Anne Marieke D. Van Stalborch, Leonie A.E. Woerdeman, Mat J.A.P. Daemen, Peter L. Hordijk, Stephan Huveneers*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)2059-2067
Number of pages9
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume34
Issue number9
DOIs
Publication statusPublished - 1 Jan 2014

Cite this

Van Geemen, D., Smeets, M. W. J., Van Stalborch, A. M. D., Woerdeman, L. A. E., Daemen, M. J. A. P., Hordijk, P. L., & Huveneers, S. (2014). F-actin-anchored focal adhesions distinguish endothelial phenotypes of human arteries and veins. Arteriosclerosis, Thrombosis, and Vascular Biology, 34(9), 2059-2067. https://doi.org/10.1161/ATVBAHA.114.304180