Shear stress patterns affect the secreted chemokine profile in endothelial cells
Issue title: Selected articles of the 30th Annual Conference of the German Society for Clinical Microcirculation and Hemorheology (DGKMH), 18–21 June, 2011, Munich, Germany
Affiliations: Department of Cardiology and Angiology, University of Erlangen-Nuremberg, Erlangen, Germany
Note: [] These authors contributed equally to this work.
Note: [] Corresponding author: Iwona Cicha, PhD, Laboratory of Molecular Cardiology, Department of Cardiology and Angiology, University of Erlangen-Nuremberg, Schwabachanlage 10, 91054 Erlangen, Germany. Tel.: +49 9131 8535896; Fax: +49 9131 8532079; E-mail: Iwona_Cicha@yahoo.com These authors contributed equally to this work.
Abstract: Background: Atherosclerotic plaques are initiated by pro-inflammatory endothelial activation at arterial regions subjected to non-uniform shear stress. We applied the in vitro flow-through cell culture slides to investigate whether different patterns of shear stress affect the secreted cytokine and chemokine profile in endothelial cells. Methods: Human umbilical vein endothelial cells (ECs) were exposed to 24 h of flow in straight or bifurcating flow-through slides, in some experiments followed by 6 h stimulation with 2.5 ng/mL TNF-α. IL-1β, IL-6, IL-8, IL-12p70, MIP-1α, MCP-1and sICAM-1 were measured in conditioned medium samples by flow cytometry using antibodies conjugated with fluorescent beads. Results: The release of IL-1β, IL-12p70 and MIP-1α from endothelial cells exposed to shear stress was below detectable levels. Strongly increased level of sICAM and significantly increased IL-8 concentration were detected in conditioned medium from endothelial cells exposed to flow in bifurcating slides as compared with cells grown under laminar flow in straight channels. The release of IL-6 and MCP-1 was not significantly induced in bifurcating slides. Treatment with TNF-α for 6 h induced 2–3 fold increase in secreted chemokines and cytokines. In particular, significantly increased MCP-1 and increased IL-8 levels were released from endothelial cells grown in bifurcating slides. This release was partly prevented in cells grown in straight channels, i.e. under exposure to laminar flow only. Conclusions: Although the endothelial monolayer areas exposed to non-uniform shear stress are relatively small, the activation of cells in these regions is strong enough to produce a detectable change in cytokine and chemokine profile, which represents the earliest step in atherogenic endothelial dysfunction.
