Abstract
Binding of endothelial cell (EC) integrins to extracellular-matrix (ECM) components is one of the key events to trigger intracellular signaling that will ultimately result in proper vascular development. Even within one tissue, the endothelial phenotype differs between arteries and veins. Here, we tested the hypothesis that anchorage-dependent processes, such as proliferation, viability, survival and actin organization of venous (VEC) and arterial EC (AEC) differently depend on ECM proteins. Moreover, because of different oxygen tension in AEC and VEC, we tested oxygen as a co-modulator of ECM effects. Primary human placental VEC and AEC were grown in collagens I and IV, fibronectin, laminin, gelatin and uncoated plates and exposed to 12 and 21% oxygen. Our main findings revealed that VEC are more sensitive than AEC to changes in the ECM composition. Proliferation and survival of VEC, in contrast to AEC, were profoundly increased by the presence of collagen I and fibronectin when compared with gelatin or uncoated plates. These effects were reversed by inhibition of focal adhesion kinase (Fak) and modulated by oxygen. VEC were more susceptible to the oxygen-dependent ECM effects than AEC. However, no differential ECM effect on actin organization was observed between the two cell types. These data provide first evidence that AEC and VEC from the same vascular loop respond differently to ECM and oxygen in a Fak-dependent manner.
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Acknowledgments
The authors are grateful to Heimo Strohmaier and Heike Knausz, from the Flow Cytometry Core Facility, and to Eleonore Fröhlich and Markus Absenger from the Microscopy Core Facility of the Center of Medical Research, Graz, Austria, for their expert technical assistance. LL received a PhD fellowship for Molecular Medicine from the Medical University Graz. UH and GD were supported by funds of the Oesterreichische Nationalbank (Anniversary Fund, project numbers: 13307 to UH, 10053, 12601 to GD). AH received funding from the Austrian Science Fund (FWF, Grant number P22521-B18).
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G. Desoye and U. Hiden contributed equally to this work.
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Lassance, L., Miedl, H., Konya, V. et al. Differential response of arterial and venous endothelial cells to extracellular matrix is modulated by oxygen. Histochem Cell Biol 137, 641–655 (2012). https://doi.org/10.1007/s00418-012-0917-4
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DOI: https://doi.org/10.1007/s00418-012-0917-4