Telmisartan prevents VCAM-1 induction and monocytic cell adhesion to endothelium exposed to non-uniform shear stress and TNF-α
Issue title: Selected Presentations from the 29th Conference of the German Society for Clinical Hemorheolgy and Microcirculation, Freie Universität Berlin, Germany, 17–18 September 2010
Affiliations: Department of Cardiology and Angiology, University of Erlangen-Nuremberg, Erlangen, Germany
Note: [] These authors contributed equally to this work. 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
Note: [] These authors contributed equally to this work.
Abstract: Background: Atherosclerotic plaques develop at arterial regions subjected to non-uniform shear stress, and are initiated by increased leukocyte-endothelial interactions. Here we applied the in vitro model of arterial bifurcations to investigate whether telmisartan, an anti-inflammatory angiotensin II receptor blocker with PPAR-gamma activating ability, prevents monocyte recruitment by endothelium. Methods: Human umbilical vein endothelial cells (ECs) were exposed to 18 h non-uniform shear stress in bifurcating flow-through slides, followed by 2 h stimulation with 2.5 ng/mL TNF-alpha. During flow, cells were treated with telmisartan. To study cell adhesion, ECs were perfused with medium containing THP-1 monocytic cells. Adherent THP-1 monocytes were quantified by light microscopy. Endothelial protein expression was determined by immunofluorescence. Results: Non-uniform shear stress in combination with TNF-alpha dramatically induced monocytic cell recruitment by endothelial cells. In cells treated with telmisartan (0.5–2.5 μmol/L) during exposure to non-uniform shear stress, dose-dependent inhibition of monocytic cell adhesion was observed, with about 45% reduction at 1 μmol/L. This effect was mediated by a significant reduction of endothelial VCAM-1 expression. On the contrary, the induction of E-selectin by TNF-alpha in ECs exposed to non-uniform shear stress was not affected by telmisartan. The inhibitory effect of telmisartan on monocytic cell recruitment and VCAM-1 induction was prevented in the presence of the PPAR-gamma antagonist GW9662. Conclusions: Treatment with telmisartan decreases the TNF-α-induced recruitment of monocytic cells and endothelial expression of VCAM-1 in regions of non-uniform shear stress in vitro. This mechanism can contribute to the beneficial pleiotropic effects of telmisartan in atherosclerosis-prone arterial regions.
